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Design, synthesis and antimicrobial activities of thiouracil derivatives

Design, synthesis and antimicrobial activities of thiouracil...

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中国化学会第九届全国有机化学学术会议

作者： Penglei Cui Yan'en Wang Huiyun Duan Hua Chen xiaoliu lia Binghe Wang Key Laboratory of Chemical Biology of Hebei Province College of Chemistry and Environmental Science Hebei University Department of Chemistry and Center for Biotechnology and Drug Design Georgia State University

The infection disease caused by bacterial pathogens has become a major public health problem in recent years due to wide occurrence of drug resistance. There is an urgent need to develop new antimicrobial agents, especially those with a new drug target and/or those that can overcome drug resistance. In bacterial cell, over 30% proteins become functional after they were transported outside of the cytoplasm. Trans-membrane movement of most of these proteins is via the Sec pathway(i.e. secretion pathway). Sec A is one of the essential components in the Sec machinery which provides a major pathway to help protein translocation from the cytosol across or into the cytoplasmic membrane1]. Because Sec A is a conserved and an essential protein in all bacteria, it is considered as a promising antibacterial drug target. In recent years, studies have confirmed that bacteria can be restrained by inhibiting Sec A2]. Therefore, developing innovative antibacterial drugs targeted on Sec A has drawn many attentions. Using the known Sec A inhibitor — symmetrical dithiouracil compound 1 as parent compound, we would like to herein report the synthesis of its derivatives bearing acyl thiourea and its antimicrobial activity against five bacteria and four fungi.

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