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Phytomedicinal aspects of sesquiterpenoid peroxides: Origin, structures and biological activity

Siddiq A

Department of Pharmacology, University of Karachi, Karachi 75270, Pakistan

Yaremenko I

N.D. Zelinsky Institute of Organic Chemistry, Russian Academy of Sciences, Leninsky Prospect 47, Moscow, Russia, 119991

Terent’ev AO

N.D. Zelinsky Institute of Organic Chemistry, Russian Academy of Sciences, Leninsky Prospect 47, Moscow, Russia, 119991

Gloriozova TA

Institute of Biomedical Chemistry, Russian Academy of Sciences, Moscow, Russia, 119121

Dzhemileva LU

Institute of Petrochemistry and Catalysis, Russian Academy of Sciences, Ufa, Russia, 450075

D’yakonov AV

Institute of Petrochemistry and Catalysis, Russian Academy of Sciences, Ufa, Russia, 450075

Vil V

N.D. Zelinsky Institute of Organic Chemistry, Russian Academy of Sciences, Leninsky Prospect 47, Moscow, Russia, 119991

Dembitsky VM

N.D. Zelinsky Institute of Organic Chemistry, Russian Academy of Sciences, Leninsky Prospect 47, Moscow, Russia, 119991

Institute of Petrochemistry and Catalysis, Russian Academy of Sciences, Ufa, Russia, 450075

DOI: 10.15761/FDCCR.1000134

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Abstract

Sesquiterpenoid peroxides are a rare group of natural metabolites isolated predominantly from various parts of plants. The biological activity of sesquiterpene peroxides has hardly been studied. This review provides information on the biological activity of 80 natural sesquiterpene peroxides. All isolated chemical compounds are divided into two groups. The first group includes sesquiterpene hydroperoxides and the second group includes sesquiterpene lactone endoperoxides. To determine the biological activity of sesquiterpene peroxides, we used the computer PASS program, which contains more than 1,000,000 natural and synthetic chemicals that exhibit more than 10,000 different activities. As shown by the analysis of these compounds, sesquiterpene peroxides are inhibitors of cell adhesion and also demonstrate antiulcer activity. In addition, individual representatives of sesquiterpene hydroperoxides showed antineoplastic and antimetastatic activity. On the other hand, sesquiterpene lactone endoperoxides demonstrated anti-inflammatory and antiprotozoal properties. The new data presented showed that sesquiterpene peroxides are an interesting group of natural medicinal preparations that can be used in pharmacology, medicine and related fields.

Key words

Hydroperoxides, endoperoxides, plant, sesquiterpenoids, activity

Introduction

Natural sesquiterpenoids are known to consist of three isoprene units and can be acyclic or contain up to three rings including many different combinations [1-5]. These compounds are found in various parts of plants [6-17], insects [18,19], and marine algae and invertebrates [1,2,20,21], and are also produced by fungal species [22,23] and bacteria [24]. Sesquiterpenoid peroxides are a rare group of natural drugs, and these compounds are produced by microorganisms and are also found in marine algae and invertebrates, fungi and of plants [25-32].

To study the activity of natural sesquiterpenoid peroxides, we used the PASS program, which contains information about a million chemical compounds and more than 10,000 biological activities of both natural and synthetic compounds [33]. The algorithm for practical use of PASS has been described in detail in several publications [34-37]. In the literature, there are few such articles that link the structure of natural sesquiterpenoids and their biological activity [38-40]. As a rule, the PASS program used in 95% confirms the activity of compounds obtained by extensive in vivo or in vitro and also provides an opportunity to see a wider range of biological activities for an individual metabolite.

This review is devoted to an interesting group of natural sesquiterpenoid peroxides and the study of their predicted biological activity.

Sesquiterpenoid hydroperoxides

Acyclic terpenes as a rare group of natural hydroperoxides (1-6, structures are shown in Figure 1, and activity is shown in Table 1) and also the davanone type hydroperoxides, (7-12) including arteincultone (7) and epi-arteincultone (8) were found in the aerial parts of flowering plants Artemisia abrotanum [41]. Arteincultone (7) was also recovered from extracts of A. herba-alba [42] and Artemisia aucheri and it showed strong anticancer activity against the MCF-7, SK-N-MC and A2780 cell lines with IC50 values of 8.5, 9.6 and 10.9 µg/mL, respectively [43], and modest antimalarial activity against Plasmodium falciparum [44,45].

Figure 1. Bioactive sesquiterpene hydroperoxides derived from plants

Table 1. Predicted biological activity of sesquiterpenoid hydroperoxides

No.

Predicted biological activity, (Pa)*

1

Antiulcerative (0,861); Cell adhesion molecule inhibitor (0,811); Hypolipemic (0,744); Antineoplastic (0,711) 

Antifungal (0,680); Apoptosis agonist (0,645); Antiprotozoal (0,613); Antiinflammatory (0,595); Immunosuppressant (0,575)

2

Antineoplastic (0,877); Apoptosis agonist (0,786); Antiprotozoal (Plasmodium) (0,653); Cell adhesion molecule inhibitor (0,646) 

Antipsoriatic (0,635); Antieczematic (0,601); Antiulcerative (0,600); Antiinflammatory (0,527) 

3

Cell adhesion molecule inhibitor (0,901); Antineoplastic (0,896); Apoptosis agonist (0,778); Antiprotozoal (Plasmodium) (0,710) 

Antipsoriatic (0,662); Antiulcerative (0,651); Antieczematic (0,627); Antiinflammatory (0,615); Hepatic disorders treatment (0,565) 

4

Cell adhesion molecule inhibitor (0,873); Antineoplastic (0,826); Antiulcerative (0,789); Hepatic disorders treatment (0,741) 

Apoptosis agonist (0,696); Antieczematic (0,684); Antiprotozoal (0,676); Antiinflammatory (0,636); Immunosuppressant (0,621)  

5

Antiulcerative (0,860); Cell adhesion molecule inhibitor (0,824); Hypolipemic (0,728); Antineoplastic (0,700) 

Antiinflammatory (0,664); Antifungal (0,619); Gastric antisecretory (0,542); Antiprotozoal (Plasmodium) (0,532) 

6

Cell adhesion molecule inhibitor (0,874); Antineoplastic (0,863); Antiinflammatory (0,728); Antiulcerative (0,685) 

Antieczematic (0,646); Antipsoriatic (0,624); Hypolipemic (0,588); Antifungal (0,562); Apoptosis agonist (0,561) 

7

Antineoplastic (0,897); Antimetastatic (0,651); Antiprotozoal (0,641); Antipsoriatic (0,598); Hypolipemic (0,582) 

8

Antineoplastic (0,897); Antimetastatic (0,651); Antiprotozoal (0,641); Antipsoriatic (0,598); Hypolipemic (0,582) 

9

Antiprotozoal (Plasmodium) (0,914); Antineoplastic (0,840); Hypolipemic (0,693); Apoptosis agonist (0,576) 

10

Apoptosis agonist (0,797); Antieczematic (0,799); Antineoplastic (0,773); Antifungal (0,624); Antiulcerative (0,615) 

Genital warts treatment (0,630); Immunosuppressant (0,602); Hypolipemic (0,573) 

11

Antieczematic (0,890); Antineoplastic (0,880); Apoptosis agonist (0,792); Genital warts treatment (0,682) 

Angiogenesis stimulant (0,672); Antipsoriatic (0,645); Immunosuppressant (0,604); Antifungal (0,539); Hypolipemic (0,512) 

12

Antieczematic (0,883); Antineoplastic (0,810); Apoptosis agonist (0,704); Genital warts treatment (0,675) 

13

Antineoplastic (0,882); Antieczematic (0,682); Immunosuppressant (0,675); Carminative (0,620); Hypolipemic (0,610) 

Apoptosis agonist (0,575); Antiulcerative (0,541); Antiinflammatory (0,538) 

14

Antieczematic (0,827); Antineoplastic (0,804); Immunosuppressant (0,619); Antipsoriatic (0,614); Apoptosis agonist (0,565) 

15

Antiulcerative (0,850); Antieczematic (0,751); Antineoplastic (0,710); Immunosuppressant (0,689); Apoptosis agonist (0,638) 

16

Antineoplastic (0,886); Antiulcerative (0,859); Apoptosis agonist (0,796); Antimetastatic (0,738); Antieczematic (0,738) 

Vasoprotector (0,713); Respiratory analeptic (0,682); Antiinflammatory (0,682); Antihelmintic (0,666); Hepatic disorders treatment (0,646); Antithrombotic (0,634); Antioxidant (0,618); Antipsoriatic (0,578); Dementia treatment (0,552); Antifungal (0,545) 

17

Antiulcerative (0,798); Antineoplastic (0,731); Carminative (0,657); Immunosuppressant (0,654); Hypolipemic (0,594) 

18

Antiinflammatory (0,895); Antineoplastic (0,877); Antiulcerative (0,761); Antimetastatic (0,726); Antifungal (0,706) 

Apoptosis agonist (0,660); Antibacterial (0,614); Antioxidant (0,610); Antithrombotic (0,562) 

Proliferative diseases treatment (0,552); Antiprotozoal (Plasmodium) (0,540) 

19

Renin release stimulant (0,874); Antineoplastic (0,766); Allergic conjunctivitis treatment (0,638); Nitric oxide scavenger (0,623)  

20

Hypolipemic (0,614); Antieczematic (0,566); Allergic conjunctivitis treatment (0,553); Antiulcerative (0,528)  

21

Antineoplastic (0,710); Immunosuppressant (0,650); Hypolipemic (0,621); Dermatologic (0,606); Antieczematic (0,582) 

Antiinflammatory (0,557); Apoptosis agonist (0,509); Prostate disorders treatment (0,500) 

22

Antineoplastic (0,865); Immunosuppressant (0,734); Antieczematic (0,709); Antidiabetic symptomatic (0,707) 

Ovulation inhibitor (0,594); Antiprotozoal (Plasmodium) (0,591); Prostate disorders treatment (0,570); Antiinflammatory (0,534) 

23

Antieczematic (0,888); Antineoplastic (0,784); Immunosuppressant (0,697); Apoptosis agonist (0,641); Antipsoriatic (0,577) 

Ovulation inhibitor (0,544); Chemoprotective (0,516); Erythropoiesis stimulant (0,516) 

*Only activities with Pa > 0.5 are shown

Hydroperoxide called litseaverticillol E (13) was detected in the extracts of the leaves and twigs of Litsea verticillata and structure was confirmed by synthesis [46,47]. Two bisabolane-type sesquiterpenes called peroxylippidulcine A (14) and B (15) were isolated from the aerial parts of Lippia dulcis [48]. The aerial parts of Carthamus lanatus afforded two oxygenated bisabolane fucoside (16) [49], and bisabolene derivative (17) was found from the aerial parts of Achillea clavennae [50]. The Carthamus glaucus known as the glaucous star thistle contained bisabolene fucopyranoside (18) [51]. Two isomeric sesquiterpene hydroperoxides called santalane (19) and isocampherenane (20) were isolated from a dichloromethane extract of Illicium tsangii [52-54]. A eudesmane derivative hydroperoxygynuradiene (21) has been obtained from the root of Gynura bicolor [55]. The aerial parts of Aster spathulifolius was the source for cytotoxic sesquiterpene hydroperoxide, 7β-hydroperoxyeudesma-11-en-4-ol (22) [56,57], and compound (23) was discovered from two plant species Xylopia emarginata and Ecdysanthera rosea, respectively [58,59].

The eudesmene-type sesquiterpene peroxide called kandenol C (24, structure are shown in Figure 2, and activity is shown in Table 2) produced by Streptomyces sp. derived from the mangrove plant Kandelia candel [60]. The aerial parts of the flowering plants in the family Asteraceae, Inula japonica contained eudesmane sesquiterpenoid (25) [61]. Hydroperoxide of dihydroartemisinic acid (26) was isolated from the plant Artemisia annua (Wallaart et al., 1999), and compound (27) was isolated from leaves of Cacalia tangutica [62], and the Mexican tree Robinsonecio gerberifolius afforted hydroperoxide (28) [63]. Hydroperoxyeudesmane cinnamate (29) and compound (39) were found in extracts of Brintonia discoidea [64], and Verbesina subcordata [65].

Figure 2. Structures of sesquiterpene hydroperoxides derived from plants

Table 2. Predicted biological activity of sesquiterpenoid hydroperoxides

No.

Predicted biological activity, (Pa)*

24

Antineoplastic (0,829); Immunosuppressant (0,725); Antieczematic (0,690); Allergic conjunctivitis treatment (0,548) 

Genital warts treatment (0,538); Dermatologic (0,535); Antiinflammatory (0,506) 

25

Antieczematic (0,817); Antineoplastic (0,805); Immunosuppressant (0,742); Antiinflammatory (0,699); Apoptosis agonist (0,625) 

Hepatoprotectant (0,596); Antifungal (0,538); Antisecretoric (0,522); Antipsoriatic (0,519); Ovulation inhibitor (0,513) 

26

Antiprotozoal (Plasmodium) (0,785); Antineoplastic (0,770); Antieczematic (0,726); Immunosuppressant (0,705) 

Antiinflammatory (0,703); Fibrinolytic (0,611); Prostate disorders treatment (0,606); Antiseborrheic (0,559) 

27

Antineoplastic (0,788); Antieczematic (0,723); Antiseborrheic (0,706); Vasoprotector (0,681); Immunosuppressant (0,673)

Antiinflammatory (0,621); Ovulation inhibitor (0,606); Hypolipemic (0,592); Alopecia treatment (0,544); Apoptosis agonist (0,544)

Genital warts treatment (0,589); Antipruritic, allergic (0,516); Endometrios treatment (0,511); Antinephrotoxic (0,506) 

28

Antineoplastic (0,857); Apoptosis agonist (0,697); Antiinflammatory (0,675); Immunosuppressant (0,663); Hypolipemic (0,629) 

29

Antieczematic (0,879); Antineoplastic (0,760); Immunosuppressant (0,736); Antiprotozoal (Plasmodium) (0,653) 

Antipsoriatic (0,562); Ovulation inhibitor (0,555); Prostate disorders treatment (0,543); Respiratory analeptic (0,523) 

30

Antineoplastic (0,904); Apoptosis agonist (0,738); Immunosuppressant (0,734); Antiinflammatory (0,721); Antifungal (0,716) 

Antieczematic (0,649); Hepatoprotectant (0,603); Cytostatic (0,562); Antibacterial (0,538); Antiprotozoal (Plasmodium) (0,538)  

31

Antineoplastic (0,821); Antiinflammatory (0,714); Apoptosis agonist (0,664); Antifungal (0,650); Hypolipemic (0,643) 

Immunosuppressant (0,614); Cytostatic (0,580); Hepatoprotectant (0,578); Dermatologic (0,557); Antibacterial (0,550) 

32

Antineoplastic (0,885); Immunosuppressant (0,740); Antieczematic (0,731); Antifungal (0,601); Antiinflammatory (0,567) 

Antidiabetic (0,560); Apoptosis agonist (0,556); Antiprotozoal (Plasmodium) (0,554); Erythropoiesis stimulant (0,547) 

33

Antineoplastic (0,736); Hypolipemic (0,660); Dermatologic (0,616); Immunosuppressant (0,526); Cholesterol antagonist (0,523) 

34

Renin release stimulant (0,756); Antineoplastic (0,677); Dermatologic (0,624); General pump inhibitor (0,550)  

35

Antineoplastic (0,857); Carminative (0,725); Antieczematic (0,714); Antiprotozoal (Plasmodium) (0,695); Antileukemic (0,622)

Immunosuppressant (0,600); Antipruritic, allergic (0,591); Antimitotic (0,572); Antipsoriatic (0,544) 

36

Antineoplastic (0,900); Antieczematic (0,891); Apoptosis agonist (0,831); Antiprotozoal (Plasmodium) (0,827) 

Antiinflammatory (0,705); Antileukemic (0,649); Immunosuppressant (0,629); Cytostatic (0,581); Antimetastatic (0,580) 

37

Antineoplastic (0,918); Antieczematic (0,891); Antiprotozoal (Plasmodium) (0,868); Apoptosis agonist (0,841) 

Antiinflammatory (0,715); Antileukemic (0,660); Immunosuppressant (0,631); Antimetastatic (0,579); Cytostatic (0,512) 

38

Antineoplastic (0,925); Antiprotozoal (Plasmodium) (0,855); Antieczematic (0,835); Apoptosis agonist (0,771)

Antiinflammatory (0,709); Antimetastatic (0,697); Cytostatic (0,692); Immunosuppressant (0,683); Antileukemic (0,656) 

39

Apoptosis agonist (0,906); Antineoplastic (0,905); Antieczematic (0,904); Antiprotozoal (Plasmodium) (0,775) 

Cytostatic (0,766); Antileukemic (0,720); Immunosuppressant (0,680); Antiinflammatory (0,596); Antimetastatic (0,556)  

40

Antineoplastic (0,918); Antieczematic (0,897); Apoptosis agonist (0,810); Antiprotozoal (Plasmodium) (0,744) 

Immunosuppressant (0,712); Antipsoriatic (0,682); Antileukemic (0,668); Antiinflammatory (0,627); Cytostatic (0,622)

Antifungal (0,598); Genital warts treatment (0,589); Antibacterial (0,527); Bone diseases treatment (0,511) 

41

Antieczematic (0,940); Antineoplastic (0,896); Antipsoriatic (0,701); Immunosuppressant (0,694); Antiprotozoal (Plasmodium) (0,679); Apoptosis agonist (0,642); Antiosteoporotic (0,628); Ovulation inhibitor (0,579); Prostate disorders treatment (0,576) 

42

Antineoplastic (0,862); Antieczematic (0,845); Apoptosis agonist (0,790); Antiprotozoal (Plasmodium) (0,714) 

Antiinflammatory (0,709); Immunosuppressant (0,673); Cytostatic (0,631); Antifungal (0,508); Antibacterial (0,501) 

43

Antieczematic (0,856); Antineoplastic (0,819); Antiprotozoal (Plasmodium) (0,737); Apoptosis agonist (0,693) 

Immunosuppressant (0,607); Antiinflammatory (0,603); Cytostatic (0,582); Antimetastatic (0,533) 

44

Antineoplastic (0,891); Antieczematic (0,822); Apoptosis agonist (0,779); Antiinflammatory (0,761); Immunosuppressant (0,698) 

Antifungal (0,667); Antiprotozoal (Plasmodium) (0,659); Antileukemic (0,526); Dermatologic (0,526) 

45

Antieczematic (0,838); Antineoplastic (0,829); Antiprotozoal (Plasmodium) (0,749); Immunosuppressant (0,726)

Cytostatic (0,724); Antiinflammatory (0,710); Antiulcerative (0,662); Apoptosis agonist (0,607); Antimetastatic (0,603) 

Antifungal (0,585); Antileukemic (0,527); Antihelmintic (0,510); Antipsoriatic (0,507) 

46

Antineoplastic (0,939); Antieczematic (0,863); Antiinflammatory (0,804); Antimitotic (0,776); Immunosuppressant (0,655) 

Antiprotozoal (Plasmodium) (0,650); Apoptosis agonist (0,612); Genital warts treatment (0,600); Prostate disorders treatment (0,570) 

47

Antineoplastic (0,951); Cytostatic (0,896); Antieczematic (0,881); Apoptosis agonist (0,880); Antiprotozoal (Plasmodium) (0,845) 

Antileukemic (0,829); Immunosuppressant (0,726); Antiinflammatory (0,720); Antimetastatic (0,665); Antiparasitic (0,655) 

Antipsoriatic (0,652); Antifungal (0,596); Antibacterial (0,590); Prostate cancer treatment (0,541) 

48

Antineoplastic (0,945); Antieczematic (0,919); Apoptosis agonist (0,915); Cytostatic (0,904); Antileukemic (0,796) 

Antiinflammatory (0,778); Antiprotozoal (Plasmodium) (0,772); Antifungal (0,761); Antiparasitic (0,749); Antipsoriatic (0,726) 

Immunosuppressant (0,699); Antibacterial (0,689); DNA synthesis inhibitor (0,503) 

49

Antineoplastic (0,955); Apoptosis agonist (0,885); Antieczematic (0,843); Cytostatic (0,723); Antiprotozoal (Plasmodium) (0,718) 

Immunosuppressant (0,714); Antiinflammatory (0,710); Antimitotic (0,684); Antileukemic (0,582); Antifungal (0,521)  

50

Antineoplastic (0,903); Antieczematic (0,798); Antiinflammatory (0,711); Immunosuppressant (0,644); Antifungal (0,632) 

Antiprotozoal (Plasmodium) (0,591); Apoptosis agonist (0,585); Cytostatic (0,527) 

*Only activities with Pa > 0.5 are shown

Series of eudesmone hydroperoxides (30-35) have been found and isolated from Epaltes divericata [66], E. mexicana [67], Pluchea arguta [68], P. symphytifolia [69], and P. quitoc [70]. Hydroperoxide (36) was isolated as an unstable oil from Artemisia herba-alba subsp. herba-alba and Ursinia tenuifolia [71], and Artemisia barrelieri [72,73]. Peroxide (37) was isolated from the aerial parts of Chrysanthemum lavandulifolium [74], and germacranolide (38) was detected in the leaves of Artemisia ludoviciana [75]. A germacranolide hydroperoxide (40) was identified from the leaves of Mulgedium tataricum [76], and the eudesmanolide (41) has been isolated from Atractylodes macrocephala [77].

Sesquiterpene lactone called tanaparthin α-peroxide (42) was discovered in the Tanacetum parthenium [78,79], and more recently found in Achillea nobilis [80]. The 8β,12-guaianolide hydroperoxide (43) was obtained from Geigeria plumose [81], compound (44) was recovered from Xanthium pungens [82], and α-peroxyachifolide (45) [83]. A hydroperoxysesquiterpene lactone called crispolide (46) was isolated from the aerial parts of Tanacetum vulgare var. crispum and from two T. vulgare chemotypes [84]. The 6α,12-germacranolide (47) was found in the leaves of Artemisia herba-alba [42], and peroxycostunolide (48) was detected in Tanacetum argentum [85]. Highly oxygenated sesquiterpene lactone (49) was isolated from Centaurea hermannii [86], and guaianolide (50) was found in Anthemis carpatica [87].

Sesquiterpene endoperoxides

Endoperoxy cuparene-type sesquiterpenoids (51-53, structures are shown in Figure 3, and activity is shown in Table 3) were identified from the Japanese liverwort Jungermannia infusca [88,89]. The chamigranes called merulin B (54) and C (55) have been found in an extract of the culture broth of a Thai mangrove-derived fungus [90,91]. Sesquiterpenoid called okundoperoxide (56) with antiplasmodial activity was detected in extracts of the plants from the family Cyperaceae, Scleria striatinux [92]. Two muurolane sesquiterpene endoperoxides, 1,4-peroxymuurol-5-ene (57) and 1,4-peroxy-5-hydroxy-muurol-6-ene (58) have been obtained from Illicium tsangii (family Schisandraceae) [52-54]. The hydroperoxide called schisansphene A (59) was isolated from the plant Schisandra sphenanthera known as magnolia berry [93].

Figure 3. Bioactive sesquiterpene endoperoxides derived from plants and fungal endophytes

Table 3. Predicted biological activity of sesquiterpenoid endoperoxides

No.

Predicted biological activity, (Pa)*

51

Antiinflammatory (0,958); Antiprotozoal (Plasmodium) (0,936); Antineoplastic (0,932); Antieczematic (0,634) 

Antifungal (Candida) (0,630); Apoptosis agonist (0,617); Cardiovascular analeptic (0,557); Gynecological disorders treatment (0,509) 

52

Antiinflammatory (0,958); Antiprotozoal (Plasmodium) (0,936); Antineoplastic (0,932); Antieczematic (0,634) 

Antifungal (Candida) (0,630); Apoptosis agonist (0,617); Cardiovascular analeptic (0,557) 

53

Antiprotozoal (Plasmodium) (0,954); Apoptosis agonist (0,910); Antineoplastic (0,768); Antimetastatic (0,587) 

Antiparasitic (0,553); Antidyskinetic (0,547); Dermatologic (0,523); Atherosclerosis treatment (0,520); Ovulation inhibitor (0,517) 

54

Antiprotozoal (Plasmodium) (0,928); Antineoplastic (0,681); Antiinflammatory (0,544); Genital warts treatment (0,516)

55

Antiprotozoal (Plasmodium) (0,928); Antineoplastic (0,681); Antiinflammatory (0,544); Genital warts treatment (0,516)

56

Antiprotozoal (Plasmodium) (0,951); Antineoplastic (0,730); Antieczematic (0,659); Antifungal (0,500) 

57

Antiprotozoal (Plasmodium) (0,908); Carminative (0,788); Antineoplastic (0,714); Antieczematic (0,587); Antimetastatic (0,584) 

Antiparasitic (0,565); Antiinflammatory (0,540); Antiviral (Arbovirus) (0,524); Antidyskinetic (0,517); Antihelmintic (0,514) 

58

Antiinflammatory (0,934); Antiprotozoal (Plasmodium) (0,879); Antineoplastic (0,866); Antieczematic (0,775) 

Antiparasitic (0,649); Antimetastatic (0,623); Antihelmintic (0,609); Fibrinolytic (0,582); Genital warts treatment (0,571)  

59

Antiinflammatory (0,945); Antiprotozoal (Plasmodium) (0,916); Antineoplastic (0,854); Antieczematic (0,700) 

Cardiovascular analeptic (0,651); Antifungal (0,544); Dementia treatment (0,540); Antiseborrheic (0,514); Antinephrotoxic (0,513) 

60

Antiprotozoal (Plasmodium) (0,965); Antineoplastic (0,792); Antieczematic (0,665); Carminative (0,652); Antimetastatic (0,584) 

Antiparasitic (0,576); Dermatologic (0,537); Antileukemic (0,519); Ovulation inhibitor (0,518); Antinephrotoxic (0,503) 

61

Antiprotozoal (Plasmodium) (0,954); Carminative (0,832); Antieczematic (0,794); Antischistosomal (0,566); Apoptosis agonist (0,565); Antifungal (Cryptococcus) (0,549); Allergic conjunctivitis treatment (0,547); Antifungal (0,533) 

62

Antiprotozoal (Plasmodium) (0,956); Antieczematic (0,700); Antineoplastic (0,670); Antifungal (0,593); Antimetastatic (0,587) 

Antiparasitic (0,574); Analgesic (0,541); Antinephrotoxic (0,520); Carminative (0,514); Antibacterial (0,510) 

63

Antiprotozoal (Plasmodium) (0,964); Apoptosis agonist (0,862); Antineoplastic (0,694); Antiseborrheic (0,576)  

64

Antiprotozoal (Plasmodium) (0,945); Antieczematic (0,715); Carminative (0,599); Antineoplastic (sarcoma) (0,529) 

65

Antiprotozoal (Plasmodium) (0,881); Antieczematic (0,734); Immunosuppressant (0,705); Cardiovascular analeptic (0,687) 

Antipruritic (0,644); Antidyskinetic (0,628); Antifungal (0,603); Antineoplastic (0,599); Antinephrotoxic (0,598)

Spasmolytic, urinary (0,576); Dementia treatment (0,570); Antiseborrheic (0,545); Vasoprotector (0,536) 

66

Antiprotozoal (Plasmodium) (0,884); Antineoplastic (0,862); Antieczematic (0,861); Apoptosis agonist (0,795) 

Antiinflammatory (0,679); Antiparasitic (0,672); Cytostatic (0,667); Antifungal (0,565); Antileukemic (0,539) 

67

Antiprotozoal (Plasmodium) (0,967); Antineoplastic (0,911); Apoptosis agonist (0,883); Antieczematic (0,836) 

Antifungal (0,812); Antiparasitic (0,811); Antiprotozoal (Leishmania) (0,731); Antiinflammatory (0,725); Immunosuppressant (0,675) 

Antischistosomal (0,668); Antibacterial (0,667); Antihelmintic (0,664); DNA synthesis inhibitor (0,652)

68

Antiprotozoal (Plasmodium) (0,925); Antineoplastic (0,914); Antieczematic (0,851); Cardiovascular analeptic (0,775) 

Antiparasitic (0,741); Antinephrotoxic (0,715); Antihelmintic (0,702); Antiinflammatory (0,702); Immunosuppressant (0,667); Genital warts treatment (0,660); Antiviral (Arbovirus) (0,641); Cytostatic (0,616); Dementia treatment (0,539) 

69

Analgesic (0,883); Carminative (0,860); Antineoplastic (0,787); Antiprotozoal (Plasmodium) (0,739); Antieczematic (0,678)

Antiparasitic (0,662); Antihelmintic (0,627); Antiseborrheic (0,617); Genital warts treatment (0,600); Antimetastatic (0,591)  

70

Antineoplastic (0,855); Analgesic (0,843); Carminative (0,841); Antiprotozoal (Plasmodium) (0,739); Antieczematic (0,654) 

Antiinflammatory (0,648); Prostate cancer treatment (0,641); Apoptosis agonist (0,594); Genital warts treatment (0,583)

71

Antiprotozoal (Plasmodium) (0,917); Antineoplastic (0,797); Antieczematic (0,768); Carminative (0,724); Antiinflammatory (0,697) 

Prostate cancer treatment (0,650); Antifungal (0,639); Immunosuppressant (0,609); Genital warts treatment (0,583)

72

Antiprotozoal (Plasmodium) (0,889); Antineoplastic (0,769); Antieczematic (0,651); Angiogenesis stimulant (0,644) 

Allergic conjunctivitis treatment (0,574); Antibacterial (0,542); Antifungal (0,528); Ovulation inhibitor (0,522) 

73

Antiprotozoal (Plasmodium) (0,936); Antineoplastic (0,912); Apoptosis agonist (0,890); Cytostatic (0,870); Antieczematic (0,831) 

Antiparasitic (0,774); Antiinflammatory (0,770); Antifungal (0,687); Chemopreventive (0,671); Antibacterial (0,656)

74

Antiprotozoal (Plasmodium) (0,939); Antineoplastic (0,898); Antieczematic (0,825); Apoptosis agonist (0,741); Antiparasitic (0,716) 

Antiinflammatory (0,690); Antifungal (0,646); Angiogenesis inhibitor (0,609); Antibacterial (0,576); Antihelmintic (0,558)  

75

Antiprotozoal (Plasmodium) (0,933); Antieczematic (0,919); Antineoplastic (0,885); Antiinflammatory (0,713) 

Antifungal (0,690); Cardiovascular analeptic (0,657); Immunosuppressant (0,637); Ovulation inhibitor (0,636) 

Antipsoriatic (0,630); Prostate disorders treatment (0,588); Antinephrotoxic (0,579); Antimetastatic (0,568)  

76

Antiinflammatory (0,949); Antineoplastic (0,946); Antieczematic (0,896); Apoptosis agonist (0,782); Antiprotozoal (Plasmodium) (0,752); Antipsoriatic (0,678); Alopecia treatment (0,665); Respiratory analeptic (0,643); Neuroprotector (0,638)

Hepatoprotectant (0,632); Immunosuppressant (0,608); Ovulation inhibitor (0,602); Dementia treatment (0,533) 

77

Antiprotozoal (Plasmodium) (0,842); Antihelmintic (0,784); Antiparasitic (0,783); Antieczematic (0,709); Antiviral (Arbovirus) (0,645); Antimetastatic (0,628); Hypolipemic (0,603); Antifungal (0,533); Antineoplastic (0,528)

78

Antiprotozoal (Plasmodium) (0,842); Antihelmintic (0,784); Antiparasitic (0,783); Antieczematic (0,709); Antiviral (Arbovirus) (0,645); Antimetastatic (0,628); Hypolipemic (0,603); Antifungal (0,533); Antineoplastic (0,528)

79

Antiprotozoal (Plasmodium) (0,922); Antineoplastic (0,917); Cardiovascular analeptic (0,895); Antieczematic (0,869) 

Antiparasitic (0,746); Antiinflammatory (0,726); Antihelmintic (0,696); Antinephrotoxic (0,695); Dementia treatment (0,541) 

*Only activities with Pa > 0.5 are shown

Highly oxygenated sesquiterpene (+)-muurolan-4,7-peroxide (60) was found in the essential oil of the liverwort Plagiochila asplenioides [94], and two sesquiterpene endoperoxides (61 and 62) were isolated from the aerial parts of the invasive plant Eupatorium adenophorum [95,96]. Unusual endoperoxide (63) was detected in the Ligularia veitchiana [97], compound (64) was isolated from the leaves of Eupatorium adenophorum [98], and metabolite (65) was found in extracts of the Xylopia emarginata [58]. The aerial parts of Montanoa hibiscifolia afforded rare endoperoxide (66) [99].

The xanthane-type sesquiterpenoid, 4β,5β-epoxyxanthatin-1α,4α-endoperoxide (67) was found in the aerial parts of Xanthium strumarium [100], and sesquiterpene lactone (68) was detected in the extract of the aerial parts of Artemisia diffusa [101]. An antimalarial guaiane endoperoxide, nardoperoxide (69) and related endoperoxide (70) were isolated from the roots of Nardostachys chinensis [102,103], and the sesquiterpene peroxide (71) has been found from the aerial parts of Croton arboreous [104]. Endoperoxide, 1α,8α-epidioxy-4α-hydroxy-5αH-guai-7(11),9-dien-12,8-olide (72) was isolated from Curcuma wenyujin with anti-influenza viral activity [105].

The aerial parts of Achillea setacea afforded endoperoxide (73) [106]. The flowering plant from the sunflower family, Pulicaria undulata contained sesquiterpene peroxy lactone (74) [107]. Artemisia annua afforded a rare seven-membered endoperoxide lactone arteannuin H (75) [108,109], and allohimachalane peroxide (76) has been obtained from Illicium tsangii [52-54].

Two diastereoisomers of a sesquiterpene endoperoxide 3,6-epidioxy-1,10-bisaboladiene (77 and 78) were obtained from the both essential oil and dichloromethane extract of the aerial parts of Senecio ventanensis [110].

An unusual sesquiterpene lactone with endoperoxide group, called tehranolide (79) with strong antimalarial activity has been discovered in many Iranian Artemisia species: A. aucheri, A. austriaca, A. biennis, A. campestris, A. deserti, A. diffusa, A. gypsacea, A. haussknechtii, A. kermanensis, A. kopetdaghensis, A. kulbadica, A. oliveriana, A. persica, A. santolina, A. sieberi, A. tschernieviana, A. ciniformis, A. incana, A. turanica and A. tournefortiana [111].

Conclusion

The presented review is devoted to a rare group of sesquiterpenoid peroxides, which are found in various parts of plants or fungal endophytes isolated from plants are produced. This group contains hydroperoxides and endoperoxides which demonstrate a wide range of biological activities. So, hydroperoxides show predominantly antitumor and antiulcer activity, and antiprotozoal and anti-inflammatory activities are characteristic for endoperoxides.

Conflicts of interest

We wish to confirm that there are no known conflicts of interest associated with this publication and there has been no significant financial support for this work that could have influenced its outcome.

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Editorial Information

Editor-in-Chief

A.A. Altintas
University Essen, Germany

Ozgur KARCIOGLU
University of Health Sciences, Turkey

Article Type

Review Article

Publication history

Received date: September 18, 2019
Accepted date: October 02, 2019
Published date: October 10, 2019

Copyright

©2019 Dembitsky VM. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited

Citation

Siddiq A, Yaremenko I, Terent’ev AO, Gloriozova TA, Dzhemileva LU4, et al. (2019) Phytomedicinal aspects of sesquiterpenoid peroxides: Origin, structures and biological activity. Frontiers Drug Chemistry Clinical Res. 2: DOI: 10.15761/FDCCR.1000134

Corresponding author

Valery M. Dembitsky

N.D. Zelinsky Institute of Organic Chemistry, Russian Academy of Sciences, Leninsky Prospect 47, Moscow, 119991, Russia

E-mail : bhuvaneswari.bibleraaj@uhsm.nhs.uk

Figure 1. Bioactive sesquiterpene hydroperoxides derived from plants

Figure 2. Structures of sesquiterpene hydroperoxides derived from plants

Figure 3. Bioactive sesquiterpene endoperoxides derived from plants and fungal endophytes

Table 1. Predicted biological activity of sesquiterpenoid hydroperoxides

No.

Predicted biological activity, (Pa)*

1

Antiulcerative (0,861); Cell adhesion molecule inhibitor (0,811); Hypolipemic (0,744); Antineoplastic (0,711) 

Antifungal (0,680); Apoptosis agonist (0,645); Antiprotozoal (0,613); Antiinflammatory (0,595); Immunosuppressant (0,575)

2

Antineoplastic (0,877); Apoptosis agonist (0,786); Antiprotozoal (Plasmodium) (0,653); Cell adhesion molecule inhibitor (0,646) 

Antipsoriatic (0,635); Antieczematic (0,601); Antiulcerative (0,600); Antiinflammatory (0,527) 

3

Cell adhesion molecule inhibitor (0,901); Antineoplastic (0,896); Apoptosis agonist (0,778); Antiprotozoal (Plasmodium) (0,710) 

Antipsoriatic (0,662); Antiulcerative (0,651); Antieczematic (0,627); Antiinflammatory (0,615); Hepatic disorders treatment (0,565) 

4

Cell adhesion molecule inhibitor (0,873); Antineoplastic (0,826); Antiulcerative (0,789); Hepatic disorders treatment (0,741) 

Apoptosis agonist (0,696); Antieczematic (0,684); Antiprotozoal (0,676); Antiinflammatory (0,636); Immunosuppressant (0,621)  

5

Antiulcerative (0,860); Cell adhesion molecule inhibitor (0,824); Hypolipemic (0,728); Antineoplastic (0,700) 

Antiinflammatory (0,664); Antifungal (0,619); Gastric antisecretory (0,542); Antiprotozoal (Plasmodium) (0,532) 

6

Cell adhesion molecule inhibitor (0,874); Antineoplastic (0,863); Antiinflammatory (0,728); Antiulcerative (0,685) 

Antieczematic (0,646); Antipsoriatic (0,624); Hypolipemic (0,588); Antifungal (0,562); Apoptosis agonist (0,561) 

7

Antineoplastic (0,897); Antimetastatic (0,651); Antiprotozoal (0,641); Antipsoriatic (0,598); Hypolipemic (0,582) 

8

Antineoplastic (0,897); Antimetastatic (0,651); Antiprotozoal (0,641); Antipsoriatic (0,598); Hypolipemic (0,582) 

9

Antiprotozoal (Plasmodium) (0,914); Antineoplastic (0,840); Hypolipemic (0,693); Apoptosis agonist (0,576) 

10

Apoptosis agonist (0,797); Antieczematic (0,799); Antineoplastic (0,773); Antifungal (0,624); Antiulcerative (0,615) 

Genital warts treatment (0,630); Immunosuppressant (0,602); Hypolipemic (0,573) 

11

Antieczematic (0,890); Antineoplastic (0,880); Apoptosis agonist (0,792); Genital warts treatment (0,682) 

Angiogenesis stimulant (0,672); Antipsoriatic (0,645); Immunosuppressant (0,604); Antifungal (0,539); Hypolipemic (0,512) 

12

Antieczematic (0,883); Antineoplastic (0,810); Apoptosis agonist (0,704); Genital warts treatment (0,675) 

13

Antineoplastic (0,882); Antieczematic (0,682); Immunosuppressant (0,675); Carminative (0,620); Hypolipemic (0,610) 

Apoptosis agonist (0,575); Antiulcerative (0,541); Antiinflammatory (0,538) 

14

Antieczematic (0,827); Antineoplastic (0,804); Immunosuppressant (0,619); Antipsoriatic (0,614); Apoptosis agonist (0,565) 

15

Antiulcerative (0,850); Antieczematic (0,751); Antineoplastic (0,710); Immunosuppressant (0,689); Apoptosis agonist (0,638) 

16

Antineoplastic (0,886); Antiulcerative (0,859); Apoptosis agonist (0,796); Antimetastatic (0,738); Antieczematic (0,738) 

Vasoprotector (0,713); Respiratory analeptic (0,682); Antiinflammatory (0,682); Antihelmintic (0,666); Hepatic disorders treatment (0,646); Antithrombotic (0,634); Antioxidant (0,618); Antipsoriatic (0,578); Dementia treatment (0,552); Antifungal (0,545) 

17

Antiulcerative (0,798); Antineoplastic (0,731); Carminative (0,657); Immunosuppressant (0,654); Hypolipemic (0,594) 

18

Antiinflammatory (0,895); Antineoplastic (0,877); Antiulcerative (0,761); Antimetastatic (0,726); Antifungal (0,706) 

Apoptosis agonist (0,660); Antibacterial (0,614); Antioxidant (0,610); Antithrombotic (0,562) 

Proliferative diseases treatment (0,552); Antiprotozoal (Plasmodium) (0,540) 

19

Renin release stimulant (0,874); Antineoplastic (0,766); Allergic conjunctivitis treatment (0,638); Nitric oxide scavenger (0,623)  

20

Hypolipemic (0,614); Antieczematic (0,566); Allergic conjunctivitis treatment (0,553); Antiulcerative (0,528)  

21

Antineoplastic (0,710); Immunosuppressant (0,650); Hypolipemic (0,621); Dermatologic (0,606); Antieczematic (0,582) 

Antiinflammatory (0,557); Apoptosis agonist (0,509); Prostate disorders treatment (0,500) 

22

Antineoplastic (0,865); Immunosuppressant (0,734); Antieczematic (0,709); Antidiabetic symptomatic (0,707) 

Ovulation inhibitor (0,594); Antiprotozoal (Plasmodium) (0,591); Prostate disorders treatment (0,570); Antiinflammatory (0,534) 

23

Antieczematic (0,888); Antineoplastic (0,784); Immunosuppressant (0,697); Apoptosis agonist (0,641); Antipsoriatic (0,577) 

Ovulation inhibitor (0,544); Chemoprotective (0,516); Erythropoiesis stimulant (0,516) 

*Only activities with Pa > 0.5 are shown

Table 2. Predicted biological activity of sesquiterpenoid hydroperoxides

No.

Predicted biological activity, (Pa)*

24

Antineoplastic (0,829); Immunosuppressant (0,725); Antieczematic (0,690); Allergic conjunctivitis treatment (0,548) 

Genital warts treatment (0,538); Dermatologic (0,535); Antiinflammatory (0,506) 

25

Antieczematic (0,817); Antineoplastic (0,805); Immunosuppressant (0,742); Antiinflammatory (0,699); Apoptosis agonist (0,625) 

Hepatoprotectant (0,596); Antifungal (0,538); Antisecretoric (0,522); Antipsoriatic (0,519); Ovulation inhibitor (0,513) 

26

Antiprotozoal (Plasmodium) (0,785); Antineoplastic (0,770); Antieczematic (0,726); Immunosuppressant (0,705) 

Antiinflammatory (0,703); Fibrinolytic (0,611); Prostate disorders treatment (0,606); Antiseborrheic (0,559) 

27

Antineoplastic (0,788); Antieczematic (0,723); Antiseborrheic (0,706); Vasoprotector (0,681); Immunosuppressant (0,673)

Antiinflammatory (0,621); Ovulation inhibitor (0,606); Hypolipemic (0,592); Alopecia treatment (0,544); Apoptosis agonist (0,544)

Genital warts treatment (0,589); Antipruritic, allergic (0,516); Endometrios treatment (0,511); Antinephrotoxic (0,506) 

28

Antineoplastic (0,857); Apoptosis agonist (0,697); Antiinflammatory (0,675); Immunosuppressant (0,663); Hypolipemic (0,629) 

29

Antieczematic (0,879); Antineoplastic (0,760); Immunosuppressant (0,736); Antiprotozoal (Plasmodium) (0,653) 

Antipsoriatic (0,562); Ovulation inhibitor (0,555); Prostate disorders treatment (0,543); Respiratory analeptic (0,523) 

30

Antineoplastic (0,904); Apoptosis agonist (0,738); Immunosuppressant (0,734); Antiinflammatory (0,721); Antifungal (0,716) 

Antieczematic (0,649); Hepatoprotectant (0,603); Cytostatic (0,562); Antibacterial (0,538); Antiprotozoal (Plasmodium) (0,538)  

31

Antineoplastic (0,821); Antiinflammatory (0,714); Apoptosis agonist (0,664); Antifungal (0,650); Hypolipemic (0,643) 

Immunosuppressant (0,614); Cytostatic (0,580); Hepatoprotectant (0,578); Dermatologic (0,557); Antibacterial (0,550) 

32

Antineoplastic (0,885); Immunosuppressant (0,740); Antieczematic (0,731); Antifungal (0,601); Antiinflammatory (0,567) 

Antidiabetic (0,560); Apoptosis agonist (0,556); Antiprotozoal (Plasmodium) (0,554); Erythropoiesis stimulant (0,547) 

33

Antineoplastic (0,736); Hypolipemic (0,660); Dermatologic (0,616); Immunosuppressant (0,526); Cholesterol antagonist (0,523) 

34

Renin release stimulant (0,756); Antineoplastic (0,677); Dermatologic (0,624); General pump inhibitor (0,550)  

35

Antineoplastic (0,857); Carminative (0,725); Antieczematic (0,714); Antiprotozoal (Plasmodium) (0,695); Antileukemic (0,622)

Immunosuppressant (0,600); Antipruritic, allergic (0,591); Antimitotic (0,572); Antipsoriatic (0,544) 

36

Antineoplastic (0,900); Antieczematic (0,891); Apoptosis agonist (0,831); Antiprotozoal (Plasmodium) (0,827) 

Antiinflammatory (0,705); Antileukemic (0,649); Immunosuppressant (0,629); Cytostatic (0,581); Antimetastatic (0,580) 

37

Antineoplastic (0,918); Antieczematic (0,891); Antiprotozoal (Plasmodium) (0,868); Apoptosis agonist (0,841) 

Antiinflammatory (0,715); Antileukemic (0,660); Immunosuppressant (0,631); Antimetastatic (0,579); Cytostatic (0,512) 

38

Antineoplastic (0,925); Antiprotozoal (Plasmodium) (0,855); Antieczematic (0,835); Apoptosis agonist (0,771)

Antiinflammatory (0,709); Antimetastatic (0,697); Cytostatic (0,692); Immunosuppressant (0,683); Antileukemic (0,656) 

39

Apoptosis agonist (0,906); Antineoplastic (0,905); Antieczematic (0,904); Antiprotozoal (Plasmodium) (0,775) 

Cytostatic (0,766); Antileukemic (0,720); Immunosuppressant (0,680); Antiinflammatory (0,596); Antimetastatic (0,556)  

40

Antineoplastic (0,918); Antieczematic (0,897); Apoptosis agonist (0,810); Antiprotozoal (Plasmodium) (0,744) 

Immunosuppressant (0,712); Antipsoriatic (0,682); Antileukemic (0,668); Antiinflammatory (0,627); Cytostatic (0,622)

Antifungal (0,598); Genital warts treatment (0,589); Antibacterial (0,527); Bone diseases treatment (0,511) 

41

Antieczematic (0,940); Antineoplastic (0,896); Antipsoriatic (0,701); Immunosuppressant (0,694); Antiprotozoal (Plasmodium) (0,679); Apoptosis agonist (0,642); Antiosteoporotic (0,628); Ovulation inhibitor (0,579); Prostate disorders treatment (0,576) 

42

Antineoplastic (0,862); Antieczematic (0,845); Apoptosis agonist (0,790); Antiprotozoal (Plasmodium) (0,714) 

Antiinflammatory (0,709); Immunosuppressant (0,673); Cytostatic (0,631); Antifungal (0,508); Antibacterial (0,501) 

43

Antieczematic (0,856); Antineoplastic (0,819); Antiprotozoal (Plasmodium) (0,737); Apoptosis agonist (0,693) 

Immunosuppressant (0,607); Antiinflammatory (0,603); Cytostatic (0,582); Antimetastatic (0,533) 

44

Antineoplastic (0,891); Antieczematic (0,822); Apoptosis agonist (0,779); Antiinflammatory (0,761); Immunosuppressant (0,698) 

Antifungal (0,667); Antiprotozoal (Plasmodium) (0,659); Antileukemic (0,526); Dermatologic (0,526) 

45

Antieczematic (0,838); Antineoplastic (0,829); Antiprotozoal (Plasmodium) (0,749); Immunosuppressant (0,726)

Cytostatic (0,724); Antiinflammatory (0,710); Antiulcerative (0,662); Apoptosis agonist (0,607); Antimetastatic (0,603) 

Antifungal (0,585); Antileukemic (0,527); Antihelmintic (0,510); Antipsoriatic (0,507) 

46

Antineoplastic (0,939); Antieczematic (0,863); Antiinflammatory (0,804); Antimitotic (0,776); Immunosuppressant (0,655) 

Antiprotozoal (Plasmodium) (0,650); Apoptosis agonist (0,612); Genital warts treatment (0,600); Prostate disorders treatment (0,570) 

47

Antineoplastic (0,951); Cytostatic (0,896); Antieczematic (0,881); Apoptosis agonist (0,880); Antiprotozoal (Plasmodium) (0,845) 

Antileukemic (0,829); Immunosuppressant (0,726); Antiinflammatory (0,720); Antimetastatic (0,665); Antiparasitic (0,655) 

Antipsoriatic (0,652); Antifungal (0,596); Antibacterial (0,590); Prostate cancer treatment (0,541) 

48

Antineoplastic (0,945); Antieczematic (0,919); Apoptosis agonist (0,915); Cytostatic (0,904); Antileukemic (0,796) 

Antiinflammatory (0,778); Antiprotozoal (Plasmodium) (0,772); Antifungal (0,761); Antiparasitic (0,749); Antipsoriatic (0,726) 

Immunosuppressant (0,699); Antibacterial (0,689); DNA synthesis inhibitor (0,503) 

49

Antineoplastic (0,955); Apoptosis agonist (0,885); Antieczematic (0,843); Cytostatic (0,723); Antiprotozoal (Plasmodium) (0,718) 

Immunosuppressant (0,714); Antiinflammatory (0,710); Antimitotic (0,684); Antileukemic (0,582); Antifungal (0,521)  

50

Antineoplastic (0,903); Antieczematic (0,798); Antiinflammatory (0,711); Immunosuppressant (0,644); Antifungal (0,632) 

Antiprotozoal (Plasmodium) (0,591); Apoptosis agonist (0,585); Cytostatic (0,527) 

*Only activities with Pa > 0.5 are shown

Table 3. Predicted biological activity of sesquiterpenoid endoperoxides

No.

Predicted biological activity, (Pa)*

51

Antiinflammatory (0,958); Antiprotozoal (Plasmodium) (0,936); Antineoplastic (0,932); Antieczematic (0,634) 

Antifungal (Candida) (0,630); Apoptosis agonist (0,617); Cardiovascular analeptic (0,557); Gynecological disorders treatment (0,509) 

52

Antiinflammatory (0,958); Antiprotozoal (Plasmodium) (0,936); Antineoplastic (0,932); Antieczematic (0,634) 

Antifungal (Candida) (0,630); Apoptosis agonist (0,617); Cardiovascular analeptic (0,557) 

53

Antiprotozoal (Plasmodium) (0,954); Apoptosis agonist (0,910); Antineoplastic (0,768); Antimetastatic (0,587) 

Antiparasitic (0,553); Antidyskinetic (0,547); Dermatologic (0,523); Atherosclerosis treatment (0,520); Ovulation inhibitor (0,517) 

54

Antiprotozoal (Plasmodium) (0,928); Antineoplastic (0,681); Antiinflammatory (0,544); Genital warts treatment (0,516)

55

Antiprotozoal (Plasmodium) (0,928); Antineoplastic (0,681); Antiinflammatory (0,544); Genital warts treatment (0,516)

56

Antiprotozoal (Plasmodium) (0,951); Antineoplastic (0,730); Antieczematic (0,659); Antifungal (0,500) 

57

Antiprotozoal (Plasmodium) (0,908); Carminative (0,788); Antineoplastic (0,714); Antieczematic (0,587); Antimetastatic (0,584) 

Antiparasitic (0,565); Antiinflammatory (0,540); Antiviral (Arbovirus) (0,524); Antidyskinetic (0,517); Antihelmintic (0,514) 

58

Antiinflammatory (0,934); Antiprotozoal (Plasmodium) (0,879); Antineoplastic (0,866); Antieczematic (0,775) 

Antiparasitic (0,649); Antimetastatic (0,623); Antihelmintic (0,609); Fibrinolytic (0,582); Genital warts treatment (0,571)  

59

Antiinflammatory (0,945); Antiprotozoal (Plasmodium) (0,916); Antineoplastic (0,854); Antieczematic (0,700) 

Cardiovascular analeptic (0,651); Antifungal (0,544); Dementia treatment (0,540); Antiseborrheic (0,514); Antinephrotoxic (0,513) 

60

Antiprotozoal (Plasmodium) (0,965); Antineoplastic (0,792); Antieczematic (0,665); Carminative (0,652); Antimetastatic (0,584) 

Antiparasitic (0,576); Dermatologic (0,537); Antileukemic (0,519); Ovulation inhibitor (0,518); Antinephrotoxic (0,503) 

61

Antiprotozoal (Plasmodium) (0,954); Carminative (0,832); Antieczematic (0,794); Antischistosomal (0,566); Apoptosis agonist (0,565); Antifungal (Cryptococcus) (0,549); Allergic conjunctivitis treatment (0,547); Antifungal (0,533) 

62

Antiprotozoal (Plasmodium) (0,956); Antieczematic (0,700); Antineoplastic (0,670); Antifungal (0,593); Antimetastatic (0,587) 

Antiparasitic (0,574); Analgesic (0,541); Antinephrotoxic (0,520); Carminative (0,514); Antibacterial (0,510) 

63

Antiprotozoal (Plasmodium) (0,964); Apoptosis agonist (0,862); Antineoplastic (0,694); Antiseborrheic (0,576)  

64

Antiprotozoal (Plasmodium) (0,945); Antieczematic (0,715); Carminative (0,599); Antineoplastic (sarcoma) (0,529) 

65

Antiprotozoal (Plasmodium) (0,881); Antieczematic (0,734); Immunosuppressant (0,705); Cardiovascular analeptic (0,687) 

Antipruritic (0,644); Antidyskinetic (0,628); Antifungal (0,603); Antineoplastic (0,599); Antinephrotoxic (0,598)

Spasmolytic, urinary (0,576); Dementia treatment (0,570); Antiseborrheic (0,545); Vasoprotector (0,536) 

66

Antiprotozoal (Plasmodium) (0,884); Antineoplastic (0,862); Antieczematic (0,861); Apoptosis agonist (0,795) 

Antiinflammatory (0,679); Antiparasitic (0,672); Cytostatic (0,667); Antifungal (0,565); Antileukemic (0,539) 

67

Antiprotozoal (Plasmodium) (0,967); Antineoplastic (0,911); Apoptosis agonist (0,883); Antieczematic (0,836) 

Antifungal (0,812); Antiparasitic (0,811); Antiprotozoal (Leishmania) (0,731); Antiinflammatory (0,725); Immunosuppressant (0,675) 

Antischistosomal (0,668); Antibacterial (0,667); Antihelmintic (0,664); DNA synthesis inhibitor (0,652)

68

Antiprotozoal (Plasmodium) (0,925); Antineoplastic (0,914); Antieczematic (0,851); Cardiovascular analeptic (0,775) 

Antiparasitic (0,741); Antinephrotoxic (0,715); Antihelmintic (0,702); Antiinflammatory (0,702); Immunosuppressant (0,667); Genital warts treatment (0,660); Antiviral (Arbovirus) (0,641); Cytostatic (0,616); Dementia treatment (0,539) 

69

Analgesic (0,883); Carminative (0,860); Antineoplastic (0,787); Antiprotozoal (Plasmodium) (0,739); Antieczematic (0,678)

Antiparasitic (0,662); Antihelmintic (0,627); Antiseborrheic (0,617); Genital warts treatment (0,600); Antimetastatic (0,591)  

70

Antineoplastic (0,855); Analgesic (0,843); Carminative (0,841); Antiprotozoal (Plasmodium) (0,739); Antieczematic (0,654) 

Antiinflammatory (0,648); Prostate cancer treatment (0,641); Apoptosis agonist (0,594); Genital warts treatment (0,583)

71

Antiprotozoal (Plasmodium) (0,917); Antineoplastic (0,797); Antieczematic (0,768); Carminative (0,724); Antiinflammatory (0,697) 

Prostate cancer treatment (0,650); Antifungal (0,639); Immunosuppressant (0,609); Genital warts treatment (0,583)

72

Antiprotozoal (Plasmodium) (0,889); Antineoplastic (0,769); Antieczematic (0,651); Angiogenesis stimulant (0,644) 

Allergic conjunctivitis treatment (0,574); Antibacterial (0,542); Antifungal (0,528); Ovulation inhibitor (0,522) 

73

Antiprotozoal (Plasmodium) (0,936); Antineoplastic (0,912); Apoptosis agonist (0,890); Cytostatic (0,870); Antieczematic (0,831) 

Antiparasitic (0,774); Antiinflammatory (0,770); Antifungal (0,687); Chemopreventive (0,671); Antibacterial (0,656)

74

Antiprotozoal (Plasmodium) (0,939); Antineoplastic (0,898); Antieczematic (0,825); Apoptosis agonist (0,741); Antiparasitic (0,716) 

Antiinflammatory (0,690); Antifungal (0,646); Angiogenesis inhibitor (0,609); Antibacterial (0,576); Antihelmintic (0,558)  

75

Antiprotozoal (Plasmodium) (0,933); Antieczematic (0,919); Antineoplastic (0,885); Antiinflammatory (0,713) 

Antifungal (0,690); Cardiovascular analeptic (0,657); Immunosuppressant (0,637); Ovulation inhibitor (0,636) 

Antipsoriatic (0,630); Prostate disorders treatment (0,588); Antinephrotoxic (0,579); Antimetastatic (0,568)  

76

Antiinflammatory (0,949); Antineoplastic (0,946); Antieczematic (0,896); Apoptosis agonist (0,782); Antiprotozoal (Plasmodium) (0,752); Antipsoriatic (0,678); Alopecia treatment (0,665); Respiratory analeptic (0,643); Neuroprotector (0,638)

Hepatoprotectant (0,632); Immunosuppressant (0,608); Ovulation inhibitor (0,602); Dementia treatment (0,533) 

77

Antiprotozoal (Plasmodium) (0,842); Antihelmintic (0,784); Antiparasitic (0,783); Antieczematic (0,709); Antiviral (Arbovirus) (0,645); Antimetastatic (0,628); Hypolipemic (0,603); Antifungal (0,533); Antineoplastic (0,528)

78

Antiprotozoal (Plasmodium) (0,842); Antihelmintic (0,784); Antiparasitic (0,783); Antieczematic (0,709); Antiviral (Arbovirus) (0,645); Antimetastatic (0,628); Hypolipemic (0,603); Antifungal (0,533); Antineoplastic (0,528)

79

Antiprotozoal (Plasmodium) (0,922); Antineoplastic (0,917); Cardiovascular analeptic (0,895); Antieczematic (0,869) 

Antiparasitic (0,746); Antiinflammatory (0,726); Antihelmintic (0,696); Antinephrotoxic (0,695); Dementia treatment (0,541) 

*Only activities with Pa > 0.5 are shown