Inhibitors of SecA as Potential Antimicrobial Agents
نویسندگان
چکیده
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 analyses using HQSAR and 3-D QSAR Topomer CoMFA analyses of 4oxo-5-cyano thiouracil derivatives. In summary, introduction of polar group such as –N3 and linker groups such as –CH2-Oenhanced 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. INDEX WORDS: SecA inhibitors, Sec pathway inhibition, Thiouracil, 1, 2,4-Triazole, Novel antibacterial therapeutics, Protein translocation inhibition INHIBITORS OF SECA AS POTENTIAL ANTIMICROBIAL AGENTS
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