Planta Med 2011; 77(6): 631-640
DOI: 10.1055/s-0030-1250405
Tropical Diseases
Reviews
© Georg Thieme Verlag KG Stuttgart · New York

Natural Products Published in 2009 from Plants Traditionally Used to Treat Malaria

Joanne Bero, Joëlle Quetin-Leclercq
  • 1Pharmacognosy Research Group, Louvain Drug Research Institute, Université Catholique de Louvain, Brussels, Belgium
Further Information

Joanne Bero

Pharmacognosy Research Group
Louvain Drug Research Institute
Université Catholique de Louvain

Avenue E. Mounier 72

1200 Brussels

Belgium

Phone: +32 27 64 72 92

Fax: +32 27 64 72 93

Email: [email protected]

Publication History

received June 15, 2010 revised July 29, 2010

accepted Sept. 9, 2010

Publication Date:
19 October 2010 (online)

Table of Contents #

Abstract

Malaria is a major parasitic disease and is responsible for almost one million deaths each year in Africa. There is an urgent need to discover new active compounds. Nature and particularly plants are a potential source of new antimalarial drugs since they contain a quantity of metabolites with a great variety of structures and pharmacological activities. This review covers the compounds with antiplasmodial activity isolated from plants which have been published during 2009 organized according to their phytochemical classes. Details are given for substances with IC50 values ≤ 11 µM. Sixty-seven references are identified.

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Introduction

There were an estimated 247 million malaria cases among 3.3 billion people at risk in 2006, causing nearly a million deaths, mostly of children under 5 years (WHO, 2008). This disease, transmitted by an Anopheles mosquito, is caused by Plasmodium species. The parasite is now resistant to a number of antimalarials but plants can offer new metabolites with an original mode of action such as artemisinin from Artemisia annua which can be active on resistant strains. In this review, all antiplasmodial metabolites new or already known and isolated from plants to treat malaria and published in 2009 are described and organised according to their phytochemical classes. All the activities were determined in vitro on Plasmodium falciparum strains unless specified and bioguided fractionation was also based on this antimalarial test. Activities were assessed on different strains among which some are chloroquine sensitive (NF54, 3D7, D6, F32, D10, Ghana, TM4), chloroquine resistant (FcB1, W2, FCM29, Dd2, FCR-3) and/or multidrug resistant (K1) strains, to find effective compounds on resistant malaria. We considered that those having an IC50 ≤ 11 µM may have some interest for further development, while those with a lower activity were less interesting. That is why we only give structures for these promising compounds, the others are cited in tables. Compounds tested in vivo are also cited. We also analysed the phytochemical classes of these metabolites published in 2009 and the families of plant from which they were isolated and compared these data with those of compounds published from 2005 to 2008. Other reviews already exist for compounds published before 2005 [1], [2], [3], [4], [5], [6], [7], or before 2009 [8], [9], [10].

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Phenolic Derivatives

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Flavonoid derivatives ([Fig. 1])

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Fig. 1 Flavonoid derivatives with moderate or promising activity in vitro against various strains of Plasmodium falciparum.

The hexane extract of ground fruits of Neuraputia magnifica var. magnifica (Engl.) Emmerich (Rutaceae) was fractionated to obtain 2′-hydroxy-3,4,4′,5,6′-pentamethoxychalcone (1) which exhibited an antiplasmodial activity with an IC50 of 6.9 µM on 3D7 [11].

A new β-hydroxydihydrochalcone named (S)-elatadihydrochalcone (2) was isolated from the seedpods of Tephrosia elata Deflers. (Leguminosae) and showed antiplasmodial activity with IC50 values of 7.9 and 15.5 µM, respectively, on D6 and W2 [12].

A new isoprenylated flavone, artopeden A (3) was isolated from the bark of Artocarpus champeden Spreng. (Moraceae) and showed antiplasmodial activity with an IC50 of 0.11 µM against 3D7 [13].

Baccharis dracunculifolia D. C. (Asteraceae) contains ermanin (4) having an IC50 of 8.3 µM on D6 and of 7.0 µM on W2 [14].

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Xanthones ([Fig. 2])

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Fig. 2 Xanthones with moderate activity in vitro against various strains of Plasmodium falciparum.

Two new xanthones, butyraxanthones A and B (5 and 6), were isolated from the stem bark of Pentadesma butyracea Sabine (Clusiaceae), together with four known xanthones: xanthone I (7), rubraxanthone (8), garcinone E (9) and 3-isomangostin (10). They exhibited antiplasmodial activity against FcB1 with IC50 values of, respectively, 6.3, 5.8, 4.7, 8.3, 6.0 and 7.6 µM but were cytotoxic against a human breast cancer cell line (MCF-7) with IC50 values of, respectively, 7.3, 7.1, 9.6, 6.3, 3.2 and 2.9 µM [15].

Three xanthones: gerontoxanthone I (11), macluraxanthone (12) and formoxanthone C (13) were isolated from the stem bark of Cratoxylum maingayi Dyer (Clusiaceae) and another one [fuscaxanthone E (14)] from the fruits of Cratoxylum cochinchinense Blume (Clusiaceae). They displayed antimalarial activity against K1 with IC50 values of 4.2, 3.4, 3.0 and 7.9 µM, respectively [16].

A new xanthone, 1,5-dihydroxy-3,6-dimethoxy-2,7-diprenylxanthone (15) was obtained from Garcinia griffithii T. Anderson (Clusiaceae). It showed antiplasmodial activity with an IC50 of 7.3 µM on a Ghana strain [17].

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Coumarins ([Fig. 3])

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Fig. 3 Coumarins with moderate or promising activity in vitro against various strains of Plasmodium falciparum.

The methanolic extract of the rhizomes of Angelica purpuraefolia T. H. Chung (Apiaceae) was investigated and two natural khellactones, (+)-4′-decanoyl-cis-khellactone (16) and (+)-3′-decanoyl-cis-khellactone (17) were isolated. These two compounds were evaluated for antiplasmodial activities and showed growth inhibitory activity against D10 with IC50 values of 1.5 and 2.4 µM, respectively [18].

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Other phenolic derivatives ([Fig. 4])

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Fig. 4 Other phenolic derivatives with moderate or promising activity in vitro against various strains of Plasmodium falciparum.

Compound 18 was isolated from the dichloromethane extracts of the leaves of Piper heterophyllum Ruiz & Pav. and P. aduncum L. (Piperaceae) and exhibited activity with an IC50 of 7.0 µM on F32 [19].

The petroleum ether extract of Viola websteri Hemsl. (Violaceae) was investigated and the main antiplasmodial compound was 6-(8′Z-pentadecenyl)-salicylic acid (19) with an IC50 of 10.1 µM (D10). Given intraperitoneally, 19 showed in vivo a 63 % suppression of parasitemia in P. berghei infected mice treated at 10 mg/kg/day. When used prophylactically a suppression of 70.1 % at the same dose was recorded [20], [21].

The bioassay-guided purification of the CH2Cl2 extract of the bark of Tapirira guianensis Aubl. (Anacardiaceae) led to the isolation of two cyclic alkyl polyol derivatives: 4,6,2′-trihydroxy-6-[10′(Z)-heptadecenyl]-1-cyclohexen-2-one (20) and 1,4,6-trihydroxy-1,2′-epoxy-6-[10′(Z)-heptadecenyl]-2-cyclohexene (21). The antiplasmodial activity of a mixture of these two compounds showed an IC50 of 4.7 µM on F32 and 5.4 µM on FcB1 [22].

A new chromone, 10,11-dihydroanhydrobarakol (22), which showed antiplasmodial activity against 3D7 (IC50 = 2.3 µM), was isolated from flowers of Cassia siamea Lam. (Caesalpinaceae) [23].

Studies on Baccharis dracunculifolia D. C. (Asteraceae) allowed the isolation of viscidone (23) which showed an IC50 of 8.1 µM on D6 and of 9.8 µM on W2 [14].

Three phenolic compounds, vismione B (24), F (25) and E (26) were isolated from the fruits of Cratoxylum cochinchinense Blume (Clusiaceae) and displayed antimalarial activity against K1 with IC50 values of 1.86, 4.76 and 10.97 µM, respectively [16].

Acyl phloroglucinols [isogarcinol (27), cycloxanthochymol (28), 7-epi-isogarcinol (29), coccinone A (30), B (31), C (32), D (33) and E (34), and 7-epi-garcinol (35)] from Moronobea coccinea Aubl. (Clusiaceae) exhibited an activity with IC50 values of 3.5, 2.1, 5.1, 4.3, 5.5, 9.0, 7.0, 4.9 and 10.1 µM, respectively, on FcB1 [24].

Isoxanthochymol (36) was obtained from Garcinia griffithii T. Anderson (Clusiaceae) and showed antiplasmodial activity with an IC50 of 4.5 µM on a Ghana strain but it was also cytotoxic against MRC-5 cells (IC50 = 7.5 µM) [17].

A new phenanthrenone, 9-O-demethyltrigonostemone (37), and a new phenanthropolone (38) were isolated from the roots of Strophioblachia fimbricalyx Boerl. (Euphorbiaceae) and displayed antiplasmodial activity (IC50 values of 8.7 and 9.9 µM, respectively) against K1 [25].

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Quinones and Derivatives ([Fig. 5])

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Fig. 5 Quinones and derivatives with moderate or promising activity in vitro against various strains of Plasmodium falciparum.

Bioassay-guided fractionation of an ethanol extract of the bark of Scutia myrtina Kurz (Rhamnaceae) led to the isolation of three new anthrone–anthraquinones dimers, scutianthraquinones A (39), B (40) and C (41), one new bisanthrone–anthraquinone trimer, scutianthraquinone D (42) and the known anthraquinone, aloesaponarin I (43). These compounds exhibited antiplasmodial activities with IC50 values of 1.23, 1.14, 3.14, 3.68 and 5.58 µM, respectively, on Dd2 and 1.2, 5.4, 15.4, 5.6 and > 50 µM, respectively, on FCM29 [26].

A phytochemical study of the stem bark of Vismia laurentii De Wild. (Clusiaceae) resulted in the isolation of a known compound, vismiaquinone A (44) which showed antimalarial activity of 1.42 µM against W2 [27].

A new compound named globiferin (45) was isolated from root extracts of Cordia globifera W. W. Sm. (Boraginaceae) with cordiachrome B (46), cordiachrome C (47) and cordiaquinol C (48). Antimalarial activities (IC50) were 8.7, 6.2, 0.8 and 1.2 µM, respectively, on K1 [28].

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Terpenoids

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Sesquiterpenes ([Fig. 6])

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Fig. 6 Sesquiterpenes with moderate or promising activity in vitro against various strains of Plasmodium falciparum.

Okundoperoxide (49) was isolated by bioassay-guided fractionation from extracts of roots of Scleria striatonux de Wild. (Cyperaceae) and possessed IC50 values of 1.8, 1.8, 5.6, 4.9 µM, respectively, on W2, D6, K1, NF54 [29].

An antiplasmodial bioguided investigation of the EtOAc extract of the aerial parts of Teucrium ramosissimum Desf. (Lamiaceae) led to the isolation of homalomenol C (50). Its IC50 was 4.7 µM on FcB1 [30].

The ethyl acetate extract of Siphonochilus aethiopicus (Schweinf.) B. L. Burtt (Zingiberaceae) rhizomes was fractionated to isolate a novel furanoterpenoid (51). This compound showed antiplasmodial activity with IC50 values of 13.9 and 7.2 µM, respectively, on D10 and K1 [31].

Bioassay-guided fractionation led to the isolation of two new sesquiterpene lactones (52 and 53) from an extract of Distephanus angulifolius (DC.) H. Rob. & B. Kahn (Asteraceae). The isolated compounds showed IC50 values of 1.9 and 1.55 µM on D10 and 3.24 and 2.10 µM on W2, respectively [32].

Bioactivity-guided fractionation of the dichloromethane extract of Xanthium brasilicum Vell. (Asteraceae) resulted in the isolation of three bioactive sesquiterpene lactones: 8-epixanthatin 1β,5β-epoxide (54), and the dimers pungiolide A (55) and B (56). They showed IC50 values of 6.5, 5.0 and 6.5 µM against K1 [33].

Fractionation of the ethyl acetate extract of Carpesium cernuum L. (Asteraceae) yielded four characterised sesquiterpenoid lactones among which 11(13)-dehydroivaxillin (57) and 11-epi-ivaxillin (58) exhibited antiplasmodial activity against D10 with IC50 values of 2.0 and 9.3 µM [34].

In vivo antiplasmodial activity of 57 showed a suppression of parasitemia of 58.6 % with a dose of 2 mg/kg/day in the four-day test [35].

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Diterpenes ([Fig. 7])

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Fig. 7 Diterpenes with moderate activity in vitro against various strains of Plasmodium falciparum.

A new diterpene, 12-O-deacetyl-6-O-acetyl-19-acetyloxycoleon Q (59), and a known one (60) were isolated from the aerial parts of Anisochilus harmandii Doan (Lamiaceae) and exhibited antiplasmodial activity with IC50 values of 6.5 and 9.1 µM on K1 [36].

A known compound, caniojane (61), was isolated from the roots of Jatropha integerrima Jacq. (Euphorbiaceae) and was evaluated for its antiplasmodial activity: IC50 of 9.6 µM against K1 [37].

Baccharis dracunculifolia D. C. (Asteraceae) was shown to contain hautriwaic acid (62) and hautriwaic acid lactone (63) which had IC50 values of 9.0 and 2.5 µM, respectively, on D6 and 7.8 and 7.0 µM, respectively, on W2 [14].

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Triterpenes ([Fig. 8])

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Fig. 8 Triterpenes with moderate or promising activity in vitro against various strains of Plasmodium falciparum.

A new quassinoid named simalikalactone E (64) was extracted from Quassia amara L. (Simaroubaceae) leaves and inhibited Plasmodium falciparum with IC50 values of 24 nM on W2, 45 nM on FcB1 and 68 nM on F32 [38].

Two new quassinoids, delaumonones A (65) and B (66) were isolated from the bark of Laumoniera bruceadelpha Noot. (Simaroubaceae) and showed an antimalarial activity on 3D7 (IC50 = 0.6 and 1.1 µM) [39].

Four other quassinoids were isolated from the dichloromethane extract of Quassia amara L. (Simaroubaceae): picrasin B (67), H–J (6870). These compounds have antimalarial activities with IC50 values of, respectively, 0.8, 3.4, 2.6 and 4.2 µM on W2 [40].

Isobrucein B (71) isolated from Picrolemma sprucei Hook. f. (Simaroubaceae) was tested for its antimalarial activity against the K1 strain (IC50 = 2.1 nM) [41].

Garcihombronane D (72) was obtained from Garcinia celebica L. (Clusiaceae) and showed an activity with an IC50 of 7.7 µM on a Ghana strain [17].

Three new limonoids, ceramicines B–D (7375), were isolated from the bark of Chisocheton ceramicus Miq. (Meliaceae). Ceramicines exhibited an antiplasmodial activity with IC50 values of 0.56, 4.8 and 5.1 µM, respectively, on 3D7 [42].

A phytochemical study of the stem bark of Vismia laurentii De Wild. (Clusiaceae) resulted in the isolation of a tetracyclic triterpene, tirucalla-7,24-dien-3-one (76) which showed antimalarial activity of 1.18 µM against W2 [27].

Baccharis dracunculifolia D. C. (Asteraceae) was shown to contain 2α-hydroxyursolic acid (77) which presented an IC50 of 6.8 µM on D6 and 6.4 µM on W2 [14].

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Alkaloids

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Ornithine and lysine derivatives ([Fig. 9])

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Fig. 9 Ornithine and lysine derivatives with promising activity in vitro against various strains of Plasmodium falciparum.

Researches on Albizia schimperiana Oliv. (Leguminosae) allowed the isolation of the new bioactive macrocyclic spermine alkaloid, namely 5,14-dimethylbudmunchiamine L1 (78). This compound demonstrated antimalarial activity against D6 and W2 with IC50 values of 0.27 and 0.34 µM [43].

Four new indolizidines: prosopilosidine (79), prosopilosine (80), isoprosopilosine (81) and isoprosopilosidine (82) and a known one, juliprosopine (83) were isolated from Prosopis glandulosa Torrey var. glandulosa (Leguminosae). These compounds exhibited potent activity with IC50 values of 62, 191, 132, 67 and 350 nM, respectively, on D6 and 152, 366, 238, 192 and 604 nM, respectively, on W2. Prosopilosine also showed in vivo antimalarial activity, exhibiting 48 % suppression of parasitemia at 2 mg/kg/day/i. p. against Plasmodium berghei after 3 days of treatment [44].

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Phenylalanine and tyrosine derivatives ([Fig. 10])

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Fig. 10 Phenylalanine and tyrosine derivatives with moderate activity in vitro against various strains of Plasmodium falciparum.

A known alkaloid, cheilanthifoline (84), from Corydalis calliantha D. G. Long (Papaveraceae) showed antiplasmodial activitiy against TM4 and K1 strains with IC50 values of 2.8 and 3.8 µM, respectively [45].

The dichloromethane extract of Doryphora sassafras Endl. (Monimiaceae) was fractionated to obtain a quaternary benzylisoquinoline alkaloid, 1-(4-hydroxybenzyl)-6,7-methylenedioxy-2-methylisoquinolinium trifluoroacetate (85) which presented an antiplasmodial activity of 4.4 µM on Dd2 and 3.0 µM on 3D7 [46].

Two new dimeric alkaloids, cassiarins D (86) and E (87), which showed antiplasmodial activity against 3D7 (IC50 = 3.6 and 7.3 µM), were isolated from flowers of Cassia siamea Lam. (Caesalpinaceae) [23].

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Tryptophane derivatives ([Fig. 11])

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Fig. 11 Tryptophane derivatives with moderate or promising activity in vitro against various strains of Plasmodium falciparum.

Flinderole A (88) was isolated from Flindersia acuminata C. T.White (Rutaceae), flinderoles B–C (8990) from F. amboinensis Poir., and isoborreverine (91) and dimethylisoborreverine (92) from F. fournieri Pancher & Sebert. They have selective antimalarial activities with IC50 values of 1.42, 0.15, 0.34, 0.32 and 0.08 µM, respectively, on Dd2 while on cancer cells (HEK-293) their IC50 values were 19.97, 2.13, 9.75, 8.99 and 4.09 µM, respectively [47].

Three new alkaloids, alstiphyllanines B–D (9395), were isolated from Alstonia macrophylla Wall. (Apocynaceae) and showed antiplasmodial activity against 3D7 with IC50 values of 0.6, 10.0 and 4.5 µM, respectively [48].

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Other N-containing compounds ([Fig. 12])

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Fig. 12 Other N-containing compounds with moderate activity in vitro against various strains of Plasmodium falciparum.

Studies on the CH2Cl2/MeOH extract from the roots of the Australian tree Mitrephora diversifolia Miq. (Annonaceae) resulted in the purification of the known 5-hydroxy-6-methoxyonychine (96) which displayed IC50 values of 9.9 and 11.4 µM, respectively, on 3D7 and Dd2 [49].

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Other Metabolites ([Fig. 13])

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Fig. 13 Other metabolites with moderate or promising activity in vitro against various strains of Plasmodium falciparum.

The flower extracts of Goniothalamus laoticus (Fin. & Gagnep.) Bân (Annonaceae) were fractionated to obtain a styryllactone, (+)-3-acetylaltholactone (97). This compound was evaluated for its antiplasmodial activity against K1 (IC50 = 9.5 µM) but it showed cytotoxicity against human cancer cell lines with IC50 values of 10.6, 3.3 and 6.6 µM, respectively, on KB, BC1 and NCI-H187 [50].

A linear polyacetylenic diol (98) was isolated from Bidens pilosa L. (Asteraceae), and exhibited antiplasmodial properties in vitro with IC50 of 1.8 µM on FCR-3 as well as antimalarial activity by intravenous injection in vivo, which was carried out in mice infected with the Plasmodium berghei NK-65 strain. The average parasitemia of 32.8 % in the control red blood cells was decreased significantly to 12.1 % by the administration of 0.8 mg/kg/day of the compound for four days [51].

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Discussion and Conclusions

In traditional medicine, traditional healers use plants for the treatment of malaria or several symptoms of the disease. This review focusing on publications of 2009 shows that some promising new antimalarial compounds can be isolated by the ethnopharmacological and bioguided fractionation approaches. Various extracts of plants were fractionated to obtain 146 compounds which were evaluated for antimalarial activity in vitro. Among them, 41 possessed low (11 < IC50 < 50 µM), 65 moderate (2 < IC50 < 11 µM) and 31 promising (IC50 < 2 µM) activity in vitro against various strains of Plasmodium falciparum which is responsible for the most severe form of malaria. The activity of some of these compounds was tested against various cell lines, normal or cancer cells, but only a few of them for their in vivo antimalarial activity. Nevertheless, in these cases, the promising in vitro activities could be confirmed by in vivo tests. Among them, a phenolic compound: 6-(8′Z-pentadecenyl)-salicylic acid, a sesquiterpene lactone: 11(13)-dehydroivaxillin, a tryptophane derivative: prosopilosine, and a linear polyacetylenic diol seem promising.

Moreover, ellagic acid already isolated and tested in vitro before 2009 with an IC50 of 0.5 µM on D6 and 0.3 µM on W2 with no cytotoxicity, displayed interesting antimalarial efficacy in vivo with a parasitemia reduction of 50 % at 1.0 mg/kg/day by the intraperitoneal route. This compound could be an interesting candidate for further development [52], [53].

Among the compounds we reviewed, only a few of them exhibited a good activity and should be considered as lead compounds for further investigations ([Table 1]). In 2009, most of the highly active compounds were found in the alkaloid and terpene chemical classes, which was also the case in 2005–2008 ([Fig. 14]). The same trend was observed when considering families from which active compounds were isolated ([Fig. 15]). Most active alkaloids published in 2009 were isolated from the Leguminosae and Rutaceae families [10]. In our previous review, Leguminosae was also identified as a family allowing isolation of a significant number of active alkaloids, while Rutaceae was not found to be particulary interesting although it is a family whose activity is often due to the presence of alkaloids [6].

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Fig. 14 Number of compounds with good activity (IC50 < 2 µM) in vitro against various strains of Plasmodium falciparum, classified according to their chemical classes.

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Fig. 15 Number of compounds with good activity (IC50 < 2 µM) in vitro against various strains of Plasmodium falciparum, classified according to the plant family from which they were isolated.

Table 1 Tested compounds presenting promising activity with IC50 < 2 µM.

Chemical class

Family

Plant

Compound

IC50 (µM)

Alkaloids

Rutaceae

Flindersia acuminata C. T. White

Flinderole A

1.42 (Dd2)

Akaloids

Rutaceae

Flindersia amboinensis Poir.

Flinderole B

0.15 (Dd2)

Alkaloids

Rutaceae

Flindersia amboinensis Poir.

Flinderole C

0.34 (Dd2)

Alkaloids

Rutaceae

Flindersia fournieri Pancher & Sebert

Isoborreverine

0.32 (Dd2)

Alkaloids

Rutaceae

Flindersia fournieri Pancher & Sebert

Dimethylisoborreverine

0.08 (Dd2)

Alkaloids

Apocynaceae

Alstonia macrophylla Wall.

Alstiphyllanine B

0.60 (3D7)

Alkaloids

Leguminosae

Albizia schimperiana Oliv.

5,14-Dmethylbudmunchiamine L1

0.27 (D6)
0.34 (W2)

Alkaloids

Leguminosae

Prosopis glandulosa Torrey

Prosopilosidine

0.06 (D6)
0.15 (W2)

Alkaloids

Leguminosae

Prosopis glandulosa Torrey

Prosopilosine

0.19 (D6)
0.37 (W2)

Alkaloids

Leguminosae

Prosopis glandulosa Torrey

Isoprosopilosine

0.13 (D6)
0.24 (W2)

Alkaloids

Leguminosae

Prosopis glandulosa Torrey

Isoprosopilosidine

0.07 (D6)
0.19 (W2)

Alkaloids

Leguminosae

Prosopis glandulosa Torrey

Juliprosopine

0.35 (D6)
0.60 (W2)

Coumarins

Apiaceae

Angelica purpuraefolia Chung

(+)-4′-Decanoyl-cis-khellactone

1.5 (D10)

Flavonoids

Moraceae

Artocarpus champeden Spreng.

Artopeden

0.11 (3D7)

Other metabolites

Asteraceae

Bidens pilosa L.

Polyacetylenic diol

1.8 (FCR-3)

Other phenolic derivatives

Clusiaceae

Cratoxylum cochinchinense Blume

Vismione B

1.86 (K1)

Quinones

Boraginaceae

Cordia globifera W. W. Sm

Cordiachrome C

0.8 (K1)

Quinones

Boraginaceae

Cordia globifera W. W. Sm

Cordiaquinol C

1.2 (K1)

Quinones

Rhamnaceae

Scutia myrtina Kurz

Scutianthraquinone A

1.23 (Dd2)
1.2 (FCM29)

Quinones

Rhamnaceae

Scutia myrtina Kurz

Scutianthraquinone B

1.14 (Dd2)
5.4 (FCM29)

Quinones

Clusiaceae

Vismia laurentii De Wild.

Vismiaquinone A

1.42 (W2)

Sesquiterpenes

Cyperaceae

Scleria striatonux De Wild.

Okundoperoxide

1.8 (W2)
1.8 (D6)
5.6 (K1)
5.0 (NF54)

Sesquiterpenes

Asteraceae

Distephanus angulifolius (DC.) H. Rob. & B. Kahn

(6S,7R,8S)-14-Acetoxy-8-[2-hydroxymethylacrylate]-15-helianga-1(10),4,11(13)-trien-15-al-6,12-olide

1.90 (D10)
3.24 (W2)

Sesquiterpenes

Asteraceae

Distephanus angulifolius (DC.) H. Rob. & B. Kahn

(5R,6R,7R,8S,10S)-14-Acetoxy-8-[2-hydroxymethylacrylate]-elema-1,3,11(13)-trien-15-al-6,12-olide

1.55 (D10)
2.10 (W2)

Triterpenes

Simaroubaceae

Quassia amara L.

Simalikalactone E

0.02 (W2)
0.05 (FcB1)
0.07 (F32)

Triterpenes

Simaroubaceae

Quassia amara L.

Picrasin B

0.80 (W2)

Triterpenes

Meliaceae

Chisocheton ceramicus Miq.

Ceramicine B

0.56 (3D7)

Triterpenes

Simaroubaceae

Laumoniera bruceadelpha Noot.

Delaumonone A

0.6 (3D7)

Triterpenes

Simaroubaceae

Laumoniera bruceadelpha Noot.

Delaumonone B

1.1 (3D7)

Triterpenes

Simaroubaceae

Picrolemma sprucei Hook. f.

Isobrucein B

0.002 (K1)

Triterpenes

Clusiaceae

Vismia laurentii De Wild.

Tirucalla-7,24-dien-3-one

1.18 (W2)

The more active triterpenes were obtained from Simaroubaceae which seem to have been well studied in 2009 and were not identified as an interesting family in 2005–2008. However, other reviews confirmed that the active antimalarial molecules of the Simaroubaceae are mainly quassinoids [6], [9]. Quassinoids often displayed anticancer activity but the antimalarial activity does not seem to be correlated with the cytotoxicity [54].

When considering highly active compounds and families from which they were isolated and comparing with the results of 2005–2008, we observed that in 2009 no highly active diterpene was isolated, although this class was pointed out to be very interesting in 2005–2008. The same is observed with the Caesalpinaceae family from which they were isolated. This may be explained by the fact that one team focused in 2005–2008 on diterpenes from Caesalpinaceae leading to Kalauni et al. [55] and Linn et al. [56].

Three of the most active sesquiterpenes are lactones and were obtained from a plant of the Asteraceae family as it was the case for the “famous” artemisinin.

Among families from which most highly active compounds were isolated in 2005–2008, Menispermaceae and Asphodelaceae are not represented in 2009 while from Moraceae, only one interesting flavonoid (artopeden A) was isolated.

These observations and comparisons show that it is often difficult to assess general rules concerning interesting classes of compounds or interesting families as it may depend highly on the activity of specific research groups. Nevertheless, we can indicate that during 2009, alkaloids from the Leguminosae and Rutaceae families, quassinoids from Simaroubaceae and well-known sesquiterpene lactones from Asteraceae were described as interesting antimalarial compounds with original structures which could be considered as lead compounds for new drugs against resistant malaria.

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Supporting information

Tested phenolic derivatives, terpenic compounds, alkaloids and other metabolites presenting low or no activity in vitro against various strains of Plasmodium falciparum (Tables 1S–4S) are available as Supporting Information.

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References

Joanne Bero

Pharmacognosy Research Group
Louvain Drug Research Institute
Université Catholique de Louvain

Avenue E. Mounier 72

1200 Brussels

Belgium

Phone: +32 27 64 72 92

Fax: +32 27 64 72 93

Email: [email protected]

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References

Joanne Bero

Pharmacognosy Research Group
Louvain Drug Research Institute
Université Catholique de Louvain

Avenue E. Mounier 72

1200 Brussels

Belgium

Phone: +32 27 64 72 92

Fax: +32 27 64 72 93

Email: [email protected]

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Fig. 1 Flavonoid derivatives with moderate or promising activity in vitro against various strains of Plasmodium falciparum.

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Fig. 2 Xanthones with moderate activity in vitro against various strains of Plasmodium falciparum.

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Fig. 3 Coumarins with moderate or promising activity in vitro against various strains of Plasmodium falciparum.

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Fig. 4 Other phenolic derivatives with moderate or promising activity in vitro against various strains of Plasmodium falciparum.

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Fig. 5 Quinones and derivatives with moderate or promising activity in vitro against various strains of Plasmodium falciparum.

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Fig. 6 Sesquiterpenes with moderate or promising activity in vitro against various strains of Plasmodium falciparum.

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Fig. 7 Diterpenes with moderate activity in vitro against various strains of Plasmodium falciparum.

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Fig. 8 Triterpenes with moderate or promising activity in vitro against various strains of Plasmodium falciparum.

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Fig. 9 Ornithine and lysine derivatives with promising activity in vitro against various strains of Plasmodium falciparum.

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Fig. 10 Phenylalanine and tyrosine derivatives with moderate activity in vitro against various strains of Plasmodium falciparum.

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Fig. 11 Tryptophane derivatives with moderate or promising activity in vitro against various strains of Plasmodium falciparum.

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Fig. 12 Other N-containing compounds with moderate activity in vitro against various strains of Plasmodium falciparum.

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Fig. 13 Other metabolites with moderate or promising activity in vitro against various strains of Plasmodium falciparum.

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Fig. 14 Number of compounds with good activity (IC50 < 2 µM) in vitro against various strains of Plasmodium falciparum, classified according to their chemical classes.

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Fig. 15 Number of compounds with good activity (IC50 < 2 µM) in vitro against various strains of Plasmodium falciparum, classified according to the plant family from which they were isolated.