Vol - 4, Issue - 3, Apr-Jul 2013 ISSN: 0976-7908 Vishnoi et al...Nishi Gupta, Garima Vishnoi*, Ankita Wal, Pranay Wal Research Scholar, PSIT Kanpur. ABSTRACT Malaria is still the most

Vol - 4, Issue - 3, Apr-Jul 2013 ISSN: 0976-7908 Vishnoi et al

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PHARMA SCIENCE MONITOR

AN INTERNATIONAL JOURNAL OF PHARMACEUTICAL SCIENCES

ANTIMALARIALS FROM SEMISYNTHETIC ORIGIN

Nishi Gupta, Garima Vishnoi*, Ankita Wal, Pranay Wal

Research Scholar, PSIT Kanpur.

ABSTRACT Malaria is still the most destructive and dangerous parasitic infection in many tropical and subtropical countries. The burden of this disease is getting worse, mainly due to the increasing resistance of Plasmodium falciparum against the widely available antimalarial drugs. So, there is an urgent need for the development of new treatments for malaria. Nature and particularly plants used in traditional medicine are a potential source of new antimalarial drugs as they contain molecules with a great variety of structures and pharmacological activities. A large number of antimalarial compounds with a wide variety of structures have been isolated from plants and can play a role in the development of new antimalarial drugs. Ethnopharmacological approaches appear to be a promising way to find plant metabolites that could be used as templates for designing new derivatives with improved properties. The literature from 1998 to October 2012 is reviewed.The review present literature compilation from plant and marine extracts, alkaloids (naphthylisoquinolines,bisbenzylisoquinolines, protoberberines and aporphines, indoles, manzamines, and miscellaneous alkaloids) terpenes (sesquiterpenes, triterpenes, diterpenes, and miscellaneous terpenes) quassinoids, flavonoids, limonoids, chalcones, peptides, xanthones, Quinones and coumarines, and miscellaneous antimalarials from nature. The review also provides an outlook to recent semisynthetic approaches to antimalarial Drugs discovered from natural sources. Keywords: antiplasmodial; malaria; plant compounds; Plasmodium falciparum; traditional medicine. INTRODUCTION

Among all parasitic agents causing disease in humans, malaria is undoubtedly the single

most destructive and dangerous infectious agent in the developing world [1,2]. This vector-

borne infectious disease is a classic example of one that affects the productivity of

individuals, families and the whole society, since it causes more energy loss, more

debilitation, more loss of work capacity and more economic damage than any other

human parasitic diseases [3].

According to the World Health Organization (WHO), malaria remains a major health

problem and affects more than 225 million individuals, causing approximately 700

thousand deaths each year. Plasmodium falciparum is the most common causative

agent[4].



Malaria is commonly associated with poverty, but is also a cause of poverty and a major

hindrance to economic development. 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 5Years of age. It is widespread in tropical and subtropical regions,

including parts of the Americas, Asia and Africa. A total of 109 countries were endemic

for malaria in 2008, 45 within the WHO African region [5].Although human malaria

transmitted by female Anopheles mosquitoes has four Plasmodium species as its

aetiological agents – P. falciparum, P. vivax, P. ovale and P. malariae, the most

widespread and severe disease is caused by P. falciparum, which transiently infects the

liver before invading red blood cells of the mammalian host (Figure 1). Clinical

manifestations occur at the erythrocytic stage and can include fever, chills, prostration

and anaemia, as well as delirium, metabolic acidosis, cerebral malaria and multi-organ

system failure, which may be followed by coma and death [6-8].Quinine (1), an

aminoquinoline alkaloid isolated from the bark of Cinchona species (Rubiaceae) in 1820

by Pelletier and Caventou, is one of the oldest and most important antimalarial drugs and

is still used today. For almost three centuries, this alkaloid was the sole active principle

effective against Plamodium falciparum, and it has been considered the responsible, after

the Second World War, for the development of synthetic antimalarial drugs belonging to

the classes of 4- and 8-aminoquinolines, such as chloroquine and primaquine , among

others. Until recently, chloroquine was the only drug used for the treatment of malaria

[9,10].

Sporozoites, injected by Anopheles mosquitoes as they bite into the skin of mammalian

hosts, rapidly enter the blood circulation to reach liver hepatocytes, where they mature in

an entirely asymptomatic phase that lasts for approximately two weeks. Sporozoites of P.

vivax and P. ovale remain dormant (hypnozoites) in the human hepatocyte, where they

mature months to years later. These forms cause late malaria relapses under conditions

that are not well understood and are related to host stress and low primaquine (PQ) doses

[11]; such relapses require new drug treatment. The ideal antimalarial should destroy

sporozoites soon after they are inoculated into the vertebrate host by the mosquitoes.

However, no effective prophylactic anti-sporozoite drug is currently in use. Medicinal



plants that hamper sporozoite development in host cells have been reported and these

plants appear to act as prophylactics, as further discussed below.

Life cycle of plasmodium –

Merozoites are liberated as merosomes from liver cells and then bud off from the

hepatocytes to invade and develop in red blood cells (RBCs) [12]. In the RBCs, the

parasites undergo asexual multiplication by schizogony and release merozoites, which

invade other RBCs, thereby reinitiating the blood-stage cycle [13]. The infected RBCs

(iRBCs) are responsible for the disease symptoms, i.e., high and periodic fever

(paroxysms), headaches (common to all human malaria species) and anaemia. The

symptoms of P. falciparum include cerebral malaria and respiratory distress (life-

threatening manifestations that are related to iRBC cytoadherence on microvascular

endothelial cells), blockage of deep capillaries with neurological symptoms and death.

The pathogenesis of severe malaria is not completely understood, although

proinflammatory cytokines are known to be involved [14] and these cytokines contribute

to the suppression of erythropoiesis, particularly in infected children [15].Evidence

supports the role of type 1 pro-inflammatory cytokines that increase the expression of



adhesion molecules on vascular endothelium and iRBC sequestration [16]. Experimental

data demonstrate that E6446, a synthetic antagonist of nucleic acid-sensing tool-like

receptors (TLRs), diminishes the activation of TLR9 and prevents the increased

production of cytokines in response to Plasmodium infections, consequently preventing

severe malaria symptoms[17].

Plasmodium ovale and Plasmodium vivax can produce a dormant form, a hypnozoite,

that can cause relapses of the disease months and even years after the original disease

(relapsing malaria) because it's dormant in the liver cells. This is why it's important after

these infections to be treated with primaquine to kill the liver stages. Primaquine cannot

be used by people with a condition called G6PD-deficiency.

Established natural product antimalarial drugs-

Cinchona species are well known for their antimalarial properties and the constituent

alkaloid quinine is still acknowledged as an effective drug. Perhaps the less widely

known stereoisomer quinidine (Figure 1) is at least as potent as, and possibly more potent

than quinine [18]. The Chinese traditional treatment of malaria includes the use of

Artemisia annua (Compositae) and its active compound, artemisinin, which are currently

under considerable interest. (Figure 1) [19]. Artemisinin has a higher chemotherapeutic

index than chloroquine and is effective in chloroquine-resistant strains of human malaria

[20]. Another species used as an antimalarial drug in Chinese traditional medicine is

Dichroea febrifuga (Saxifragaceae) [21]. The active principle, febrifugine (Fig. 1) has been

used clinically against P. vivax and P. ovalebut its liver toxicity makes it unacceptable as

a useful antimalarial drug [22]. The use of plants for the treatment of malaria extends to at

least three continents including several countries in Africa [23], Americas [24] and Asia [25].

The NAPRALERT natural product database lists species from 152 genera which have

folklore reputations for antimalarial properties. It is important that using modern

biological techniques plants with these traditional representations are investigated in

order to establish their safety and efficacy, and to determine their value as the source of

new antimalarial drug.



Artemisinin Sergeolide

N

N

O

O HN

OH

FEBRIFUGINE

Figure 1 Some examples of antimalarial natural products

The discovery of the first antimalarial treatment almost 400 years ago resulted from

observations that acutely ill patients were cured of malaria after treatment with infusions

of bark obtained from plants growing in the Peruvian Amazon [26]. Such activity

in Cinchona calisaya and Cinchona succirubra plants was later attributed to the alkaloid

quinine (QN), which was characterized by French chemists in 1820. QN remains

important for treating complicated P. falciparum malaria despite its toxicity when used

for extended periods of time [27,28].

Several 4-aminoquinolines were later synthesised based on the QN ring (Table 1).

Among them, chloroquine (CQ) is the safest and least expensive drug and most



frequently was used to treat malaria worldwide as an essential component of the Global

Malaria Eradication Campaign. This campaign, launched in 1955, was based on the

treatment of malaria patients using CQ in association with mosquito control measures. In

the late 1960s, P. falciparum CQ-resistant strains appeared in Latin America and South

East Asia and gradually spread to most endemic regions. This campaign was interrupted

in the 1970s. Malaria had been eradicated in a few countries [29]. Most importantly, multi-

drug and cross-drug resistance among existing antimalarials, mainly the aminoquinolines,

were reported. CQ is now used only in drug combinations against P. falciparum or as the

schizonticide of choice to treat P. vivax and other human plasmodia species.

ANTIMALARIAL DRUG RESISTANCE-

The appearance of drug-resistance P. falciparum strains since 1960, in particular to

chloroquine, has made the treatment of malaria increasingly problematic in virtually all

malarious regions of the world [2]. Several researchers have dedicated efforts to the

development of new active compounds, especially from artemisinin (4), as an alternative

to chloroquine (2). Currently no single drug is effective for treating multi-drug resistant

malaria, and effective combination therapy includes artemisinin derivatives such as

artesunate (5), or mixtures with older drugs such as the atovaquone (6) – proguanil (7)

combination Malarone® [2,30]. Unfortunately first reports on drug resistance to

artemisinin-derivatives [31] and to drug combination therapies [32] have already appeared.

So, in the absence of a functional, safe and widely available malaria vaccine, efforts to

develop new antimalarial drugs continue being urgently needed now.

There is a consensus among the scientific community that natural products have been

playing a dominant role in the discovery of leads for the development of drugs for the

treatment of human diseases [33]. Indeed, the vast majority of the existing antimalarial

chemotherapeutic agents are based on natural products, and this fact anticipates that new

leads may certainly emerge from thetropical plant sources, since biological chemo

diversity continues to be an important source of molecular templates in the search for

antimalarial drugs [34-36].





THE PROMISE OF NATURAL PRODUCTS-

The most significant recent development in naturally occurring antimalarial drugs is

arguably the identification of artemisinin (Figure 1) as the active component of the plant

Artemisia annua,which is used in traditional medicine as an antimalarial agent [37]. This

unique sesquiterpene contains an endoperoxide group that appears to be an essential

requirement for its activity. It is particularly active in vivo against chloroquine resistant

P.falciparum and is reported to have relatively low toxicity. However, in the usual dose

of 0.6 mg/day for 3 days, the average recurrence rate is more than 10% [37]. Due to its

highly lipophilic nature, there are inherent problems with its administration as a drug and

several derivatives have been prepared, including arthemeter (methyl dihydroartemisinin)

and sodium artesunate (sodium dihyroartemisinin hemisuccinate). Artemisinin and its

two derivatives have been used clinically for the treatment of cerebral malaria in an area

where chloroquine resistance was endemic and the cure rate was greater than 90%[38].

The mode of action is not primarily at the level of nucleic acid synthesis but it appears to

inhibit protein synthesis [39].

The current review provides an overview of a great number of bioactive natural products

that have recently been described in the literature (from January 2009 to November 2010)

as showing antiplasmodial activity (in vitro), along with a few compounds that were

tested for antimalarial activity in animal models [40] using Plasmodium knowlesi (in

simians), Plasmodium yoelii, Plasmodiumberghei, Plasmodium chabaudi (in mice), and

Plasmodium gallinaceum (in birds). In most of these bioassays, antiplasmodial activities

were assessed using different P. falciparum strains, which include chloroquine-sensitive

(NF54, NF54/64, 3D7, D6, F32, D10, HB3, FCC1-HN, Ghana, MRC-02, TM4),

chloroquine-resistant (BHz26/86, Dd2, EN36, ENT30, FcB1, FCM29, FCR3, FCR-3/A2,

FCR3F86, S20,W2,), chloroquine-resistant and pyrimethamine-resistant (K1,

TM91C235), pyrimethamine-resistant (HB3), cycloguanil-resistant (CDC1), and

chloroquine- and antifolate-resistant (K1CB1). Most of evaluations used the [3H]-

hypoxanthine-incorporation assay to assess parasite inhibition of growth in the presence

of the test-drugs. Antimalarial activity of new compounds has also been determined by

using: i) the fluorometric method based on the intercalation of the fluorochrome

PicoGreen (SYBR) in the parasite DNA, [41]; ii) enzyme-linked immunosorbent assays



(ELISAs) with monoclonal antibodies, which measure the P. falciparum-specific antigen

histidine-rich protein 2 (HRP2) or lactate dehydrogenase protein (pLDH). A chemical

reaction using ferriprotoporphyrine biocrystallization (FBTI Inhibition Test) has been

used to provide a possible action mechanism for presumed antimalarial compounds [42].

Protein farnesyltransferase (FTase) bioassays have also been used to provide insight into

their mode of action against P.falciparum [43]. The effects of natural products on

glutathione (GSH), which plays a key role in redox mechanisms, and on cysteine (Cys),

which is one of the substrates needed for the de novo synthesis of P. falciparum GSH, as

well as their impact on β-hematin formation have been investigated, since GSH

participates in heme detoxification [44].

Several criteria have been proposed for considering a compound as active. Generally, a

compound is considered to be inactive when it shows an IC50 > 200 μM, whereas those

with an IC50 of 100-200 μM have low activity; IC50 of 20-100 μM, moderate activity;

IC50 of 1-20 μM good activity; and IC50 < 1 μM excellent/potent antiplasmodial activity

[45].

A total of 360 antiplasmodial natural products comprised of terpenes, including

iridoids,sesquiterpenes, diterpenes, terpenoid benzoquinones, steroids, quassinoids,

limonoids, curcubitacins, and lanostanes; flavonoids; alkaloids; peptides;

phenylalkanoids; xanthones; naphthopyrones; polyketides, including halenaquinones,

peroxides, polyacetylenes, and resorcylic acids; depsidones; benzophenones; macrolides;

and miscellaneous compounds.

Classes of natural product with antimalarial activity-

Alkaloids -

Cassiarin A (2) from the leaves of Cassia siamea (Leguminosae) showed promising

antimalarial activities. Cassiarin A had inhibitory effects against P. falciparum (IC50 =

0.02 M).Antimalarial activity was assessed in vivo using the 4-day suppressive test

procedure. The ED50 value of cassiarin A was 0.17 [46].

Acridone alkaloids have been isolated from the fruits of Zanthoxylum leprieurii

(Rutaceae), and among them arborinine (3) and xanthoxoline (4) exhibited a good in

vitro antiplasmodial activity against the P. falciparum strain 3D7, with IC50 values of

15.8 and 17.0 μM, respectively [47].



HO

N

O

2

N

O

R

OH

R

OMe

R R'

3 Me OMe

4H OMe

TERPENES-

SESQUITERPENES-

Antimalarial activity of sesquiterpene lactones from Neurolaena lobata has been

documented.[48]Bioasay-guided fractionation of the extract from the wood-decayed

fungus Xylaria sp. BCC 1067 led to the isolation of elemophilane sesquiterpenes (+)-

phaseolinone (5) and (+)-phomenone (6).[49] Sesquiterpenes 5 and 6 known as

phytotoxins exhibited promising antimalarial activity (EC50 = 0.50 and 0.32

lg/mL,respectively).

O

HO

O

OH

O

5. (+)Phaseolinone

O

HO

O

OH

6. (+)-Phomenone



TRITERPENES-

Fanta et al. reported the antiplasmodial activity of two triterpenoid saponins, glinoside A

(7) and glinoside B (8) isolated from the aerial parts of Glinus oppositifolius.[50] The

crude extracts exhibited better antiplasmodial activity (IC50 = 31.8 lg/mL) than the pure

saponins (7, IC50 = 42.3 lg/mL). An antimalarial tirucalla- type triterpene, epi-oleanolic

acid (9, IC50 = 28.3 lM) has been reported from Celaenodendron mexicanum.[51 ]A bis

nortriterpene quinone methide, 20-epi-isoiguesterinol (10) isolated from the roots of

Salacia madagascariensis showed potent activity against P. falciparum(IC50 = 68

ng/mL).[52]

O

O

OH

OH

O

HO

HO

OH

7. GlinosideA, R=OH

8. GlinosideB, R=H

COOH

H

HO

9. epi- Oleanolicacid



CH2OH

O

HO

10. 20- epi- Isoioguesterinol

DITERPENES-

Tilley et al. performed molecular modeling studies on a series of diterpene isonitriles and

isothiocyanates isolated from the tropical marine sponge Cymbastela hooperi, employing

3D-QSAR with receptor modeling methodologies.[53]These studies showed that the

modeled compounds like diisocyanoadociane (11) and axisonitrile- 3 (12) exert their

activities by: (i) inhibiting the decomposition of H2O2, (ii) inhibiting the peroxidative

destruction of FP, and the GSH-mediated breakdown of FP, and (iii) interfering with b–

hematin formation. Diisocyanoadociane (11) displayed IC50 of 14.48 nM against P.

falciparum D6 strain.

NC

H

H

H

H

H

NC

11. Diisocyanoadociane

CN

Axisonitrile-312.



OH

R1

R2

13. R1 =OH,R2=iPr

14. R1=iPr,R2=H

CH2OH

H

15. Dehydroabieetinol

H

HO

16

Clarkson et al. studied the effect of two diterpenes 13 and 14 isolated from

Harpagophytum procumbens, on erythrocyte shape to determine the selectivity of their

antiplasmodial activity.[54]It was observed that 13 and 14 did not alter erythrocyte shape

at the concentrations which resulted in the inhibition of parasite growth (0.76 and 0.95

lg/mL, respectively) or at the highest test concentration (100 lg/mL). This suggested that

the mechanism of action of these compounds is different from dehydroabietinol (15)

despite of structural similarities. Ziegler et al. have reported that antiplasmodial activity



of 15, an abietane-type diterpene from Hyptis suaveolens was due to erythrocyte

membrane modification.[55]Diterpene 15 inhibited parasite growth (IC50 = 25.6 lM) at

similar concentrations at which cytotoxicity was observed (IC50 = 28.0lM).

Miscellaneous terpenes –

Recently, Moein et al. isolated and characterized a terpene, 12,16-dideoxy aegyptinone B

(17) from the roots of Zhumeria majdae, which exhibited promising antiplasmodial

activity (IC50= 1.3 and 1.4 lg/mL against chloroquine sensitive and resistant strains,

respectively).[56]

17. 12,16-DideoxyaegyptinoneB

Flavonoid-

The exact mechanism of antimalarial action of flavonoids is unclear but some flavonoids

are shown to inhibit the influx of L-glutamine and myoinositol into infected

erythrocytes.[57]

Exiguaflavanone A (18a) and exiguaflavanone B (18b) from Artemisia indica exhibited

in vitro antiplasmodial activities (IC50= 4.6 and 7.0 lg/mL, respectively.[58]



O

HO

OH

OH O

RO

18a. ExiguaflavanoneA,R=H

18b. exiguaflavanone B,R=CH3

O

OH

HO

O

OCOCH3

OH

19

O

OH

HO

O

OCH3

20. Acacetin

(_)-cis-3-Acetoxy-40,5,7-trihydroxyflavanone (19, IC50 = 24.3 lg/mL) was isolated from

the lipophilic extract of leaves of Siparuna andina which showed higher in vitro

antimalarial activity (IC50 = 3.0 lg/mL).[59]Although obtained from an active fraction,

19 was less active (IC50 = 24.3 mg/mL). 3.32 lM against K1 and NF54 strains, obtained

from Vriesea sanguinolenta,[59] acacetin (20, IC50 = 5.5 and 12.6 lg/mL against poW

and Dd2 strain, respectively), 7-methoxyacacetin, and genkwanin isolated from A.

afra,73possessed considerable antiplasmodial activity.

Quinones-

Quinone methides 21 and 22 were isolated from the roots of Salacia kraussii. The isolates

showed high antiplasmodial activity (IC50 = 94.0 and 27.6 ng/mL, respectively).[61] The



mode of action of these furano and hydroxy-naphthoquinones appears to be the inhibition

of mitochondrial electron transport and respiratory chain by reduced oxygen consumption

similar to that of atovaquone.

HO

O

RH

21. R=CHO

22. R=COOMe

quinones

O

HO

HO

O OH

OR

COCH3HO

O

OHHO

HO

HO

23. R=

24. Knipholone, R=CH3

Phenylanthraquinones like (23) and knipholone (24) were isolated from Bulbine

frutescens.

The glycoside 23 displayed better activity than 24 (IC50 = 0.41and 0.67 lg/mL,

respectively), whose antiplasmodial activity appears to be associated intrinsically with

the complete molecular array of a phenylanthraquinone including the stereogenic axis.[62]

Xanthones-

The xanthone 1,5-dihydroxy-3,6-dimethoxy-2,7-diprenylxanthone (25) showed selective

activity against P. falciparum with an IC50 value of 7.25 μM. When screened for activity

against T. cruzi, T. brucei, L. infantum (Ghana strain), S. aureus, and E. coli, and for

cytotoxicity against MRC-5 cells, it showed IC50 values >64 μM [63]. Xanthones 26-27

and their analogues 28,29 have been isolated from Cratoxylum maingayi and Cratoxylum

cochinchinense (Clusiaceae) [64].These compounds showed antiplasmodial activity

against P. falciparum at concentrations of 11.0 to 1.9 μM. Most of these compounds also

showed cytotoxicity toward the NC1-H187 cancer cellline [64].



O

O

OMeMeO

OH

25.

O

OH

OH

OH

HO

O

26.

O O

O OH

HO

OH

27



OH OH

HO

O

OMe

28

HO

O OH OH

OMe

29

Coumarins-

Biologically guided fractionation of the methanolic extract of the roots of Zanthoxylum

flavum Vahl. (Rutaceae) led to the isolation of isoimperatorin (30) which displayed IC50

values of 5.5 and 2.7 mM against D6 and W2, respectively.[65] A new coumarinolignan

was isolated from a sample of Grewia bilamellata Gagnep. (Tiliaceae), grewin (31),

which displayed antimalarial activity against D6 and W2 (IC50 11.2 mM and 5.5 mM,

respectively) without significant sscytotoxicity.[66]shows coumarins with moderate or

promising activity in vitro against various strains of P. falciparum.



O

OOO

30.

OO

O

OH

O

OCH3

HO

HO

31

Phenols-

The petroleum ether extract of Viola websteri Hemsl.(Violaceae) was investigated and

the main antiplasmodial compound was 6-(8’Z-pentadecenyl)-salicylic acid (32) with an

IC50 of 10.1 mM (D10).[47]



OH

COOH

32.

Dictyochromenol (33) and a known compound, 2’E,6’ E 2-farnesyl hydroquinone (34)

obtained from the petroleum ether extract of the whole plant of Piper tricuspe C.DC.

(Piperaceae) showed antimalarial activity against FcB1 with IC50 values of 9.58 and

1.37 mM while the selectivity index suggests their high toxicity.[67]

O

HO

33

OH

HO

34



Lignans-

From the hexane extract of holostylis reniformis duch(aristolochiaceae)three lignans were

isolated: (7’R,8S,8’R)-4,5 dimethoxy-3’,4’-methylene dioxy-2,7’ – cyclo lignan-7-

one(35)(IC50=0.20 (IC50 = 0.26 mM), (7’R,8S,8’R)-3’,4,4’,5-tetramethoxy-2,7’-

cyclolignan-7-one (36) (IC50 =0.32 mM), (7’R,8R,8’S)-3’,4,4’,5-tetramethoxy-2,7’-

cyclolignan-7-one (37) (IC50 =0.20 mM). Most compounds possessed high

antiplasmodial activity against BHz26/86 and low toxicity on hepatic cells. Therefore,

these compounds are potential candidates for the development of antimalarial drugs.[68]

O

H3CO

H3CO

OCH3

OCH3

36

O

H3CO

H3CO

OCH3

OCH3

37

CONCLUSIONS

Medicinal plants have provided valuable and clinically used antimalarials like quinine

and artemisinin. In past few years, not only plants but fungi, bacteria and marine

organisms have also been intensively investigated for obtaining new antimalarial agents.

As discussed in this review, several compounds containing unique structural composition

have been isolated and characterized from natural sources. These natural products have

exhibited promising antimalarial activities in vitro and in vivo. However, limitations such



as toxicity, low bioavailability and/or poor solubility have restricted the scope of use for

several natural products in humans.

Nevertheless, nature provides novel leads, which can be developed into safe drugs by

synthetic strategies as exemplified by artemether, and quinoline class of antimalarials.

Therefore,compounds described herein provide useful bioactive synthons, which could be

modulated to obtain antimalarials active against not only drug-sensitive, but also drug-

resistant and multi-drug resistant strains of Plasmodium. In this direction, semisynthetic

approaches to newer and modified antimalarials have provided useful insights into their

applicability in antimalarial drug discovery.

To conclude, nature has been generous in providing several remedies for the treatment of

disease like malaria. However, still there is vast unexplored flora and fauna, which when

systematically explored will provide additional new leads and drugs for malaria

chemotherapy.

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For Correspondence: Garima Vishnoi Email: [email protected]

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Vol - 4, Issue - 3, Apr-Jul 2013 ISSN: 0976-7908 Vishnoi et al...Nishi Gupta, Garima Vishnoi*, Ankita Wal, Pranay Wal Research Scholar, PSIT Kanpur. ABSTRACT Malaria is still the most