Design, synthesis, and biological evaluation of pyrimidine analogs as SecA inhibitors

AbstractSecA, a key component of the bacterial Sec-dependent secretion pathway, is an attractive target for the development of new antimicrobial agents. We have previously reported pyrimidine analogs as SecA inhibitors. Herein, we report an extension of the earlier work in the synthesis and evaluation of a series of 15 5-cyanothiouracil derivatives as SecA inhibitors. All the compounds have been evaluated for their inhibition of SecA ATPase (EcSecAN68) and for their antimicrobial activity againstEscherichia coli NR698 (a leaky mutant) andBacillus anthracis Sterne. Twelve compounds showed IC50 of less than 6.3  μM when tested against EcSecAN68. In antimicrobial studies againstE. coli NR698, six compounds showed MIC of<12.5  μM with three being less than 6.3 μM. AgainstB. anthracis Sterne, three compounds showed MIC of<6.3  μM.
Source: Medicinal Chemistry Research - Category: Chemistry Source Type: research