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Articles

Vol. 2 No. 4 (2011): October-December 2011

Discovery of Novel and Potent Molecules against Plasmodium falciparum Farnesyltransferase (PfFT) by Improved Virtual Screening Strategy

Submitted
December 20, 2024
Published
2011-11-15

Abstract

Farnesyl transferase is an enzyme found in Plasmodium falciparum and other parasites which has been identified as pathogenic to humans. Therefore, Plasmodium falciparum Farnesyl Transferase (PfFT 3D7) has been suggested as a novel target in the development of drugs directed against parasite infections. With the aim of identifying new inhibitors for PfFT 3D7, rational approaches of drug discovery were followed. Pharmacophore models were generated based upon a series of 287 structurally diverse molecules out of which 24 were selected as training set and 263 as test set exhibiting ED50 values from 1.8 nM to 5000 nM for PfFT 3D7 protein. The model was validated by using 263 compounds as test set which had a correlation coefficient of 0.96. Enamine database containing 228,942 compounds was virtually screened and 27 compounds having the best mapping with the pharmacophore model were retrieved. These compounds with high estimated activity were analyzed and further validated by docking studies to contemplate the interaction between new hits and active site.

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