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

• Published in: Bioorganic & medicinal chemistry letters Vol. 19; no. 2; pp. 401 - 405
• Main Authors: Musonda, Chitalu C., Whitlock, Gavin A., Witty, Michael J., Brun, Reto, Kaiser, Marcel
• Format: Journal Article
• Language: English
• Published: Amsterdam Elsevier Ltd 15.01.2009; Elsevier
• Subjects: Animals; Antibiotics. Antiinfectious agents. Antiparasitic agents; Antiparasitic agents; Antiprotozoal Agents - chemical synthesis; Antiprotozoal Agents - pharmacology; Biological and medical sciences; Drug Evaluation, Preclinical; Hit-to-lead; L. donovani; Leishmania; Leishmania donovani; Leishmania donovani - drug effects; Malaria; Medical sciences; P. falciparum; Pharmacology. Drug treatments; Plasmodia; Plasmodium falciparum; Plasmodium falciparum - drug effects; Pyrimidines - chemical synthesis; Pyrimidines - pharmacology; Structure-Activity Relationship; Plasmodia; Malaria; Leishmania; P. falciparum; L. donovani; Hit-to-lead; Antimalarial; Five membered ring; Nitrogen heterocycle; Leishmania donovani; Physicochemical properties activity relationship; Pyrrolidine derivatives; Pyridine derivatives; Antiprotozoal agent; Plasmodium falciparum; Structure activity relation; Chlorine Organic compounds; Six membered ring; Chemical synthesis; Kinetoplastida; Protozoa; Apicomplexa; In vitro; Parasiticide; Property structure relationship; Lipophilicity; Physicochemical properties
• ISSN: 0960-894X; 1464-3405
• DOI: 10.1016/j.bmcl.2008.11.098

A series of 2-pyridyl pyrimidines has been shown to possess potent in vitro activity against leishmania parasites. 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.