title: 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 microg/mL except 3i which also demonstrated activity against Escherichia coli at 12.5 microg/mL concentration. Only two compounds, 3a and 3b, demonstrated antibacterial activity against Pseudomonas aeruginosa and E. coli with MIC 12.5 microg/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.
authors.affiliation: Medical Mycology and Medicinal Chemistry, Central Drug Research Institute, 226001, Lucknow, India.
authors.forename: Nidhi
authors.initials: N
authors.lastname: Agarwal
authors.forename: Pratibha
authors.initials: P
authors.lastname: Srivastava
authors.forename: Sandeep K
authors.initials: SK
authors.lastname: Raghuwanshi
authors.forename: D N
authors.initials: DN
authors.lastname: Upadhyay
authors.forename: Sudhir
authors.initials: S
authors.lastname: Sinha
authors.forename: P K
authors.initials: PK
authors.lastname: Shukla
authors.forename: Vishnu
authors.initials: V
authors.lastname: Ji Ram
mesh_terms: D000900:Anti-Bacterial Agents; D000890:Anti-Infective Agents / Q000138:chemical synthesis* / Q000494:pharmacology; D001419:Bacteria / Q000187:drug effects; D002713:Chlorine; D015195:Drug Design; D005658:Fungi / Q000187:drug effects; D008826:Microbial Sensitivity Tests; D009169:Mycobacterium tuberculosis / Q000187:drug effects; D011743:Pyrimidines / Q000138:chemical synthesis / Q000494:pharmacology*; D013329:Structure-Activity Relationship
chemical_list: D000900:Anti-Bacterial Agents; D000890:Anti-Infective Agents; D011743:Pyrimidines; D002713:Chlorine