Pharmacophore model for pentamidine analogs active against Plasmodium falciparum.

Abstract:

:Pentamidine and its analogs constitute a class of compounds that are known to be active against Plasmodium falciparum, which causes the most dangerous malarial infection. Malaria is a widespread disease known to affect hundreds of millions of people and presents a perceivable threat of spreading. Hence, there is a need for well-defined scaffolds that lead to new, effective treatment. Here we present a pentamidine-based pharmacophore constructed using GALAHAD that would aid targeted synthesis of leads with enhanced properties, as well as the development of lead scaffolds. The study was supported by high-quality biological in vitro data of 22 compounds against the P. falciparum strains NF54 and K1. The model established reveals the importance of hydrophobic phenyl rings with polar oxygen and amidine substituents and the hydrophobic linking chain for the activity against malaria.

journal_name

Eur J Med Chem

authors

Athri P,Wenzler T,Tidwell R,Bakunova SM,Wilson WD

doi

10.1016/j.ejmech.2010.09.012

subject

Has Abstract

pub_date

2010-12-01 00:00:00

pages

6147-51

issue

12

eissn

0223-5234

issn

1768-3254

pii

S0223-5234(10)00660-4

journal_volume

45

pub_type

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