Synthesis and biological evaluation of 2-aminothiazole derivatives as antimycobacterial and antiplasmodial agents

Bioorg Med Chem Lett. 2014 Jan 15;24(2):560-4. doi: 10.1016/j.bmcl.2013.12.022. Epub 2013 Dec 12.

Abstract

A series of compounds derived from the 2-amino-4-(2-pyridyl) thiazole scaffold was synthesized and tested for in vitro antimycobacterial activity against the Mycobacterium tuberculosis H37Rv strain, antiplasmodial activity against the chloroquine sensitive NF54 Plasmodium falciparum strain and cytotoxicity on a mammalian cell line. Optimal antimycobacterial activity was found with compounds with a 2-pyridyl ring at position 4 of the thiazole scaffold, a substituted phenyl ring at the 2-amino position, and an amide linker between the scaffold and the substituted phenyl. The antiplasmodial activity was best with compounds that had the phenyl ring substituted with hydrophobic electron withdrawing groups.

Keywords: 2-Amino-4-(2-pyridyl)thiazoles; Antimycobacterial; Antiplasmodial; Hit optimisation; Structure–activity relationship.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Anti-Bacterial Agents / chemical synthesis*
  • Anti-Bacterial Agents / pharmacology*
  • Antimalarials / chemical synthesis*
  • Antimalarials / pharmacology*
  • CHO Cells
  • Cricetinae
  • Cricetulus
  • Drug Evaluation, Preclinical / methods
  • Mycobacterium tuberculosis / drug effects
  • Mycobacterium tuberculosis / physiology
  • Plasmodium falciparum / drug effects
  • Plasmodium falciparum / physiology
  • Thiazoles / chemical synthesis*
  • Thiazoles / pharmacology*

Substances

  • Anti-Bacterial Agents
  • Antimalarials
  • Thiazoles
  • 2-aminothiazole