Protein translocation is essential for bacterial survival and the most important translocation mechanism in bacteria is the secretion (Sec) pathway. Thus targeting Sec pathway is a promising strategy for developing novel antibacterial therapeutics.

We report the design, syntheses, mechanistic studies and structure-activity relationship studies using HQSAR and 3-D QSAR Topomer CoMFA analyses of 4-oxo-5-cyano thiouracil derivatives. In summary, introduction of polar group such as –N₃ and linker groups such as –CH₂-O- enhanced the potency as well as logP and logS several fold.

We also report the discovery, optimization and structure-activity relationship study of 1,2,4-triazole containing pyrimidines as novel, highly potent antimicrobial agents. A number of inhibitors have been found to inhibit microbial growth at high nanomolar concentrations.