Benzoheterocyclic amodiaquine analogues with potent antiplasmodial activity: synthesis and pharmacological evaluation

Dennis S B Ongarora; Jiri Gut; Philip J Rosenthal; Collen M Masimirembwa; Kelly Chibale

doi:10.1016/j.bmcl.2012.06.010

Benzoheterocyclic amodiaquine analogues with potent antiplasmodial activity: synthesis and pharmacological evaluation

Bioorg Med Chem Lett. 2012 Aug 1;22(15):5046-50. doi: 10.1016/j.bmcl.2012.06.010. Epub 2012 Jun 9.

Authors

Dennis S B Ongarora¹, Jiri Gut, Philip J Rosenthal, Collen M Masimirembwa, Kelly Chibale

Affiliation

¹ Department of Chemistry, University of Cape Town, Rondebosch 7701, South Africa.

PMID: 22749280
DOI: 10.1016/j.bmcl.2012.06.010

Abstract

The synthesis and evaluation of antiplasmodial activity of benzothiazole, benzimidazole, benzoxazole and pyridine analogues of amodiaquine is hereby reported. Benzothiazole and benzoxazole analogues with a protonatable tertiary nitrogen atom possessed excellent activity against the W2 and K1 chloroquine resistant strains of Plasmodium falciparum, with IC(50)s ranging from 7 to 22 nM.

Publication types

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

MeSH terms

Amodiaquine / analogs & derivatives*
Amodiaquine / chemical synthesis
Amodiaquine / pharmacology
Animals
Antimalarials / chemical synthesis*
Antimalarials / chemistry
Antimalarials / pharmacology
Benzimidazoles / chemistry
Benzothiazoles / chemistry
Benzoxazoles / chemistry
Cell Line
Drug Resistance, Microbial / drug effects
Heterocyclic Compounds / chemistry
Plasmodium falciparum / drug effects
Pyridines / chemistry
Rats
Structure-Activity Relationship

Substances

Antimalarials
Benzimidazoles
Benzothiazoles
Benzoxazoles
Heterocyclic Compounds
Pyridines
Amodiaquine
benzimidazole
benzothiazole
pyridine