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Abstract

SYNTHESIS AND BIOLOGICAL EVALUATION OF PURINE NUCLEOSIDE PHOSPHORYLASE INHIBITORS FROMP. FALCIPARUM

Hitendra Kumar Lautre*, Kishor Patil, Hafid Youssouffi,Taibi Ben Hadda,Vikesh Bhatia, Ajai Kumar Pillai

ABSTRACT

Plasmodium falciparum is responsible for majority of life-threateningcases of malaria. Purine nucleoside phosphorylase in P.falciparum(PfPNP)is an important target enzyme for the treatment of malaria. It isan essential element for growth and survival of the parasite in culture.PNP catalyzes reversible phosphorolysis of purine deoxy andribonucleosides with the formation of Rib-1-P and appropriate bases.In an effort we have synthesized Zn(II), Co(II) and Cr(II) complexes of2-amino-5-nitro-N-hydroxybenzamidine. Structural characterizationswereperformed using FTIR, NMR, UV-Vis, elemental and massanalysis. These compounds were assayed for inhibition of both PfPNP and growth of parasiteP. falciparum. All the compounds were found to be moderate to good inhibitors in the rangeof IC50 values, 65μM - 115 μM against PfPNP. Their antibacterial, antifungal and DNAcleavage studies were studied to evaluate their antimicrobial activities.

Keywords: P.falciparum, Purine nucleoside phosphorylase inhibitors, 2-amino-5-nitro-Nhydroxybenzamidine.


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