Antimalarials from nature

Pentacyclic lupane-type triterpenes, exemplified by lupeol [lup-20(29)-en-3b-ol], principally found in common fruit plants such as olive, mango, strawberry, grapes, etc., were reported to possess beneficial effects as a therapeutic and preventive agent for a range of disorders. Although lupeol exhibits an array of biological activities like anti-inflammatory and anti-arthritic activities both in in vitro and in vivo systems, extensive exploration to establish its role as a chemopreventive compound is warranted. Last 15 years have seen tremendous efforts by researchers worldwide to develop this wonderful molecule for its clinical use toward the treatment of a variety of disorders. These studies also provide insight into the mechanism of action of lupeol and suggest that it is a multi-target agent with immense anti-inflammatory potential targeting key molecular pathways which involve nuclear factor kappa B (NF-jB), cFLIP, Fas, Kras, phosphatidylinositol-3-kinase in a variety of cells. It is noteworthy that lupeol at its effective therapeutic doses exhibits no toxicity to normal cells and tissues. The perception of chemoprevention lies still in its infancy. Intervention to slow down, arrest or reverse the process of carcinogenesis by the use of either natural or synthetic substances individually or in combination therapy has emerged as a promising and pragmatic medical approach to reduce cancer risk.

Biological Activities of Lupeol

The sixth annual review provides an accounting of 388 chemical libraries reported in the year 2002. Libraries are segregated into 10 tables, providing a convenient reference to libraries published with and without accompanying biological data. Three tables inventory solid-phase reagents and scavengers, linkers, and polymer-supported chiral ligands.

Comprehensive survey of combinatorial library synthesis: 2002.

Malaria caused by protozoa of the genus Plasmodium, because of its prevalence, virulence, and drug resistance, is the most serious and widespread parasitic disease encountered by mankind. The inadequate armory of drugs in widespread use for the treatment of malaria, development of strains resistant to commonly used drugs such as chloroquine, and the lack of affordable new drugs are the limiting factors in the fight against malaria. These factors underscore the continuing need of research for new classes of antimalarial agents, and a re-examination of the existing antimalarial drugs that may be effective against resistant strains. This review provides an in-depth look at the most significant progress made during the past 10 years in antimalarial drug development.

G.K Srivastava

Papers

Solid-phase synthesis and bioevaluation of lupeol-based libraries as antimalarial agents.