As malarial drug resistance increases due to mutations in the DHFR domain, it is necessary to probe the enzyme with new, more flexible chemotypes in order to develop more effective antimalarial drugs. Novel compounds have been designed with a N-phenyl triazine moiety bridged with a CH2NH linker to a hydrophobic X-phenyl group in order to overcome these mutations. A series of 4,6-diamino-1,2-dihydro-2,2-dimethyl-1-(3'-(3''-X-anilinomethyl)phenyl)-s-triazines have been synthesized and will be tested as potential inhibitors of the critical bifunctional enzyme, thymidylate synthase-dihydrofolate  reductase that is essential for the biosynthesis  of DNA, RNA, amino acids and proteins in the infectious plasmodium,  Plasmodium falciparum.

Synthesis of 4,6-diamino-1,2-dihydro-2,2-dimethyl-1-(3'-(3''-X-anilinomethyl)phenyl)-s-triazines as potential <i>Plasmodium falciparum</i> DHFR inhibitors

247th National Meeting (2014)

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Synthesis of 4,6-diamino-1,2-dihydro-2,2-dimethyl-1-(3'-(3''-X-anilinomethyl)phenyl)-s-triazines as potential Plasmodium falciparum DHFR inhibitors