Syntheses of 2,4,6-trisubstituted pyrimidine derivatives as a new class of antifilarial topoisomerase II inhibitors.

A series of 21 compounds of trisubstituted pyrimidine derivatives have been synthesized and evaluated for their in vitro topoisomerase II inhibitory activity against filarial parasite Setaria cervi. Out of these, seven compounds (8, 11-14, 25 and 28) have shown 60-80% inhibition at 40 and 20 microg/mL concentration. Five compounds (12, 13, 14, 25 and 28) exhibited 70-80% inhibition at 10 microg/mL concentration and three compounds (13, 14 and 28) have shown 40-60% inhibition at 5 microg/mL concentration. All the above mentioned compounds have shown better topo II inhibitory activity than standard antifilarial drug (DEC) and enzyme topo II inhibitors (Novobiocin, Nalidixic acid).

Perspective in antimalarial chemotherapy.

Antimalarial chemotherapy has become more complex and challenging because of multidrug resistant strains of Plasmodium falciparum. Due to resistance of malarial parasite against well known drugs, the chemotherapy of malaria has become complicated. In this review we have discussed brief introduction followed by life cycle of malaria parasite. The list of commercially available antimalarial drugs along with there action on different stages of parasite have been discussed. A brief description of their mechanism of action and advantages and disadvantages were reported. The natural products as antimalarial have been discussed in the review. On the basis of chemical classes the natural products were divided in the following categories; Quinoline alkaloids, Iso-quinoline alkaloids, Indoloquinoline alkaloids, Carbolines, Bis-isoquinoline, 4-Quinazole derivatives, Trioxanes, Terpenes, Naphthoquinone, Anthraquinones, Chalcones, Hydroxy flavanones, Coumarins and phenolic glycoside. The combination chemotherapy has been highlighted in the review. The Biochemical and Immunological changes in malarial infection are discussed along with complications of malarial chemotherapy due to resistance. In the conclusion section, the future strategies for the chemotherapy of malaria have been discussed.

Solid phase synthesis of structurally diverse tetra substituted pyrimidines for potential use in combinatorial chemistry.

A new pyrimidine based scaffold has been identified for generation of combinatorial libraries using solid phase technique. The utility of the scaffolds was demonstrated by synthesizing small libraries of 12 substituted pyrimidines (4a-4l).