Design, Synthesis and Antibacterial Activities of Triazole-Pyrimidine Derivatives as SecA Inhibitors

Abstract

Background: To highlight the magnitude of the important challenge now facing scientists, drug resistance needs exploration of novel antimicrobial agents. The identification of new and vital target in bacteria and then designing their inhibitors can be explored. Thus, targeting SecA, a central component of the bacterial general secretion system, is a promising strategy for the development of novel antimicrobials. Objective: To evaluate new compounds as SecA inhibitors synthesized by structural modification of bistriazole SCA-21. Method: A new compounds were synthesized and evaluated for antibacterial activity against <i>Escherichia coli</i> NR698 (<i>E. coli</i> a leaky mutant), <i>Staphylococcus aureus (S. aureus)</i> and <i>Bacillus anthracis (B. anthracis).</i> Results: Some novel triazole-pyrimidine derivatives by structural modification of known SecA inhibitor SCA 21 were synthesized and their structures were confirmed by ¹H NMR, ¹³C NMR and Mass spectral analysis. The synthesized compound showed antimicrobial activity against <i>E. coli</i> NR698 (a leaky mutant), <i>S. aureus</i> and <i>B. anthracis</i> Sterne. Conclusion: Five novel triazole-pyrimidine derivatives were designed, synthesized and evaluated as SecA inhibitors. At the end of this study, compound SCA 259 with azide pentyl group was found as the most potent inhibitor. It expressed better inhibitory activity against SecA ATPase than else known inhibitor SCA 21.