Chloropyrimidines as a new class of antimicrobial agents

Abstract

In the course of our investigations of pyrimidines as antimycotic agents, we have identified a sub-class, with significant in vitro activity against mycobacteria. The salient feature of these pyrimidine derivatives (3a–o and 7a,b) is their appended aryl, heteroaryl and alkylthio substituent at position 6 and also alkylthio substituent at position 2. The rational design, synthesis, and evaluation of the in vitro antibacterial activity against six pathogenic bacteria including virulent and non-virulent strains of Mycobacterium tuberculosis is described. Some of the synthesized compounds (3c, 3h, 3i, 3o) have displayed only potent in vitro antimycobacterial activity with MIC of 0.75 μg/mL except 3i which also demonstrated activity against Escherichia coli at 12.5 μg/mL concentration. Only two compounds, 3a and 3b, demonstrated antibacterial activity against Pseudomonas aeruginosa and E. coli with MIC 12.5 μg/mL. All the synthesized compounds were also evaluated for their antimycotic activity against five pathogenic fungi but only some of them 3j–n and 7a,b were found most potent against Aspergillus fumigatus and Trichophyton mentagrophytes.