The success of the antimalarial drug quinine and the discovery of artemisinin, the most potent antimalarial drug, both from plant sources, has led to the study of plants as antimalarial agents. The ethnopharmacological approach for the search of new antimalarial agents from plant sources has proved to be more predictive. This article gives a critical account of crude extracts, essential oils and secondary plant metabolites with diverse chemical structure possessing antimalarial activity against different malarial parasites. The major leads have been highlighted and some reported structure-activity relationships and their possible modes of action discussed.

Antimalarial agents from plant sources

Antimalarial activity of plant metabolites

Publisher Summary This chapter discusses the alkaloids from Malaysian flora. Malaysia is located in the heart of South East Asia and constitutes part of the Malaysian phytogeographical region. Its position near the Equator confers on it a typically tropical climate, characterized by high temperatures, humidity and rainfall throughout the year. Such conditions are conducive to plant life and have resulted in a rich and thriving flora. The potential for botanical and chemical studies and for discovery of novel chemical constituents, especially those possessing useful bioactivities is therefore immense. The need for such studies has assumed a greater urgency in recent times in the wake of the threat posed by rapid development and with the growing concern that valuable plant substances which may present useful lead compounds for drug discovery may be lost.

Alkaloids from Malaysian Flora

Publisher Summary This chapter discusses the alkaloid natural products that are particularly active against Leishmania sp ., Trypanosomacruzi, Trypanosomabrucei, and Plasmodium falciparum . The alkaloids with antiprotozoal activity are grouped according to their structures or origin in several categories such as quinoline and isoquinoline alkaloids, indole alkaloids, steroidal alkaloids, alkaloids from marine organisms, and other alkaloids. A discussion on structure-antiprotozoal activity relationships is included, and the mechanism of action of several of these metabolites is described in the chapter. Recent developments, as well as new experimental strategies in discovery and development of antiprotozoal compounds, are also discussed in the chapter. Some of the in vitro antitrypanosomal or cytotoxic activities have been transformed into molar concentrations to allow a better comparison, independent of their molecular weight. Nevertheless, direct comparison remains complex because of the different assay procedures used in various laboratories. Alkaloids are one of the most important groups of natural products, already providing many drugs for human use. Although they can be seriously toxic for the host, alkaloid-containing plants and their biosynthesized alkaloids have a remarkable potential to provide pharmaceutical and biological agents contributing to the development of future antiparasitic drugs. Natural alkaloids will continue to play an important role in the development of a new generation of antiprotozoal drugs.

Alkaloids with antiprotozoal activity.

The crude extract of the bark of Dehaasia longipedicellata exhibited antiplasmodial
 activity against the growth of Plasmodium falciparum K1 isolate (resistant strain).
 Phytochemical studies of the extract led to the isolation of six alkaloids: two
 morphinandienones, (+)-sebiferine (1) and (−)-milonine (2); two aporphines,
 (−)-boldine (3) and (−)-norboldine (4); one benzlyisoquinoline, (−)-reticuline
 (5); and one bisbenzylisoquinoline, (−)-O-O-dimethylgrisabine
 (6). Their structures were determined on the basis of 1D and 2D NMR, IR, UV, and LCMS
 spectroscopic techniques and upon comparison with literature values. Antiplasmodial activity was
 determined for all of the isolated compounds. They showed potent to moderate activity with
 IC50 values ranging from 0.031 to 30.40 µM.
 (−)-O-O-dimethylgrisabine (6) and (−)-milonine (2) were the two most
 potent compounds, with IC50 values of 0.031 and 0.097 µM, respectively, that were
 comparable to the standard, chloroquine (0.090 µM). The compounds were also assessed for their
 antioxidant activities with di(phenyl)-(2,4,6-trinitrophenyl)iminoazanium
 (IC50 = 18.40–107.31 µg/mL), reducing power (27.40–87.40 %), and metal chelating
 (IC50 = 64.30 to 257.22 µg/mL) having good to low activity.
 (−)-O-O-dimethylgrisabine (6) exhibited a potent antioxidant activity of 44.3 %
 reducing power, while di(phenyl)-(2,4,6-trinitrophenyl)iminoazanium and metal chelating
 activities had IC50 values of 18.38 and 64.30 µg/mL, respectively. Thus it may be
 considered as a good reductant with the ability to chelate metal and prevent pro-oxidant
 activity. In addition to the antiplasmodial and antioxidant activities, the isolated compounds
 were also tested for their cytotoxicity against a few cancer and normal cell lines.
 (−)-Norboldine (4) exhibited potent cytotoxicity towards pancreatic cancer cell line
 BxPC-3 with an IC50 value of 27.060 ± 1.037 µM, and all alkaloids showed no toxicity
 towards the normal pancreatic cell line (hTERT-HPNE).

J. Phillipson

Papers

Alkaloids from Dehaasia incrassata.