Synthesis and evaluation of 2-pyridyl pyrimidines with in vitro antiplasmodial and antileishmanial activity

Chitalu C Musonda; Gavin A Whitlock; Michael J Witty; Reto Brun; Marcel Kaiser

doi:10.1016/j.bmcl.2008.11.098

Synthesis and evaluation of 2-pyridyl pyrimidines with in vitro antiplasmodial and antileishmanial activity

Bioorg Med Chem Lett. 2009 Jan 15;19(2):401-5. doi: 10.1016/j.bmcl.2008.11.098. Epub 2008 Dec 3.

Authors

Chitalu C Musonda¹, Gavin A Whitlock, Michael J Witty, Reto Brun, Marcel Kaiser

Affiliation

¹ University of Cape Town, Department of Chemistry, P/B Rondebosch 7700, Cape Town, South Africa; Department of Chemistry, Pfizer Global R&D, Ramsgate Road, Sandwich, Kent CT13 9NJ, United Kingdom.

PMID: 19091562
DOI: 10.1016/j.bmcl.2008.11.098

Abstract

A series of 2-pyridyl pyrimidines, reported inhibitors of Plasmodium falciparum methionine aminopeptidase 1b were synthesized and evaluated for their antiplasmodial activities. An analysis of physicochemical properties demonstrated a link between lipophilicity and antiparasitic activity. Cross screening of the library against cultured Leishmania donovani parasites revealed this class of compounds as potent inhibitors of parasite development in vitro.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Antiprotozoal Agents / chemical synthesis*
Antiprotozoal Agents / pharmacology*
Drug Evaluation, Preclinical
Leishmania donovani / drug effects*
Plasmodium falciparum / drug effects*
Pyrimidines / chemical synthesis*
Pyrimidines / pharmacology*
Structure-Activity Relationship

Substances

Antiprotozoal Agents
Pyrimidines