Natural and Semi synthetic Antimalarial Compounds: Emphasis on the Terpene Class

Abstract

Malaria is one of the most important tropical diseases since more than 40% of the world population is at risk. This disease is endemic to more than 100 nations and remains one of the main leading causes of death in children less than five years of age worldwide. Natural product-derived compounds have played a major role in drug discovery, often as prototypes to obtain more active semi synthetic derivatives. Antimalarial pharmacotherapy is a significant example of plant-derived medicines, such as quinine and artemisinin. This review highlights studies on terpenes and their semi synthetic derivatives from natural sources with antimalarial activity reported in the literature during eleven years (2002-2013). A total of 114 compounds are found among terpenes and their semi synthetic derivatives. Cytotoxicity of the compounds is also found in this review. Furthermore, the physicochemical properties of the terpenes addressed are discussed based on seven well established descriptors, which provide a useful source for the elaboration of a terpene library of antimalarial compounds.

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“…This shows that there is no correlation between the IC 50 value obtained with the MMFM and the chloroquine sensitivity of the strain tested. This phenomenon has been described by several authors testing the anti-plasmodial activity of natural products 24,25,26 .…”

Transcriptome analysis of polycyclic sesquiterpene biosynthesis in Leonurus sibiricus L.

“…Class I TPSs ionize an isoprenoid diphosphate substrate to yield an allylic cation and inorganic pyrophosphate by assist of metal cluster whereas class II TPSs relies on a general acid (an aspartic acid side chain) to protonate the terminal carbon−carbon double bond of an isoprenoid substrate to yield a tertiary carbocation [14]. In depth, seven clades, a, b, c, d, e/f, g and h types are recognized according to TPSs amino acid sequence relativity [23,24]. Most of plant STSs belong to TPS-a subfamily.…”

Terpenes as Potential Antimalarial Drugs

“…However, not all authors described a clear explanation about their mechanism of action. Recently, Silva et al [66] listed 114 terpenes and their semisynthetic derivate with antimalarial activity, but only three have their mechanism of action elucidated. For several years, studies have been made of the large diversity of prenylated compounds biosynthesized by P. falciparum.…”