Antiprotozoal agents antimalarials

Histones of Plasmodium falciparum represent a new target for antimalarials. Apicidin [Cyclo (N-O-methyl-L-tryptophanyl-L-isoleucinyl-D-pipecolinyl-L-2-amino-oxodecanoyl] is a potent, broad spectrum antiprotozoal agent. The target of apicidin is Histone deacetylases HDA (Darkin Rattray et al., 1996), evidenced as hyperacetylation of histones in treated parasites. 

Pyrimethamine and proguanil are used as oral antimalarials.and inhibit the utilization of folate by the malarial parasite, so are valuable in chemoprophylaxis and in preventing the transmission of malaria. (See ANTIMALARIALS.) Trimethoprim is a useful antibacterial, and as an antiprotozoal in antimalarial therapy. The selectivity of these agents derives, in part, from the fact that whereas mammals can obtain folic acid from the diet, bacteria and the asexual forms of the malarial parasite must synthesize it. Also, the dihydrofolate reductase enzyme in humans is less sensitive to these drugs than that of the parasites. 

The non-classical antimetabolite approach, on the other hand, appears to have struck gold recently in the field of antimalarials as well as other antiprotozoal and antibacterial agents. If the reported animal screening results are any indication of the therapeutic usefulness of the new 2,4-diaminoquinazolines and related compounds, then one would think that the goal of eradicating these parasitic diseases is in sight. 

Marine natural products are even more poorly characterized than terrestrial plants but are no less diverse. Chemical compounds with unique and significant biological activities are being discovered with increasing frequency as this immense resource is explored. Since many of these compounds are reported to possess antiprotozoal activities, (106-108) the marine environment may be reasonably expected to yield potential antimalarial agents. 

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