Solid-phase synthetic approach towards new pyrimidines as potential antibacterial agents

Herein, we report the polymer-supported synthesis of new pyrimidine derivatives and their antimycobacterial and antimicrobial activity. Our methodology is based on the fast and efficient solid-phase synthesis having the ability to implement structural diversity from the readily available building blocks through minimum synthetic route and with high yields. Our method was validated in the synthesis of a model chemical library prepared via a combinatorial approach. All the prepared compounds were evaluated for their antimycobacterial activity against Mycobacterium tuberculosis H37Rv, antibacterial activity against Staphylococcus aureus, Pseudomonas aeruginosa, Escherichia coli, and Enterococcus faecalis, and activity against two fungal strains of Candida albicans and Aspergillus niger. Our results reveal that most of the tested compounds have modest antimycobacterial activity against M. tuberculosis H37Rv, with the most active being pyrimidine 2f (MIC value 32 mg/mL). Moreover, compound 1b showed considerable activity against P. aeruginosa. These results indicate the potential of our developed methodology that could lead to a pathway for the preparation of new drug candidates in the future. (C) 2019 Elsevier B.V. All rights reserved.