Synthesis, antibacterial activities and molecular docking study of thiouracil derivatives containing oxadiazole moiety

Abstract

A series of novel thiouracil derivatives 9 containing an oxadiazole moiety have been synthesized by structural modification of a lead SecA inhibitor, 2. These compounds have been evaluated for their antibacterial activities against Bacillus amyloliquefaciens, Staphylococcus aureus and Bacillus subtilis. Among them, compounds 9g and 9n exhibited promising antibacterial activities against the tested strains. Compound 9g was also tested for its inhibitory activities against SecA ATPase, and the IC₅₀ value of compound 9g was 19.9 μg/mL, lower than that of compound 2 (20.8 µg/mL). Molecular docking work indicates that compound 9g likely occupies the pocket formed by SecA IRA2 and NBD domain.

Graphical Abstract

Keywords:

• Antibacterial activities
• thiouracil
• molecular docking
• SecA inhibitor

Acknowledgments

We gratefully acknowledge Prof. Binghe Wang and the use of Orion that is supported by Georgia State University's Research Solutions and the free academic licensing program of Openeye. We gratefully acknowledge Prof. Liyan Yu in the Chinese Academy of Medical Sciences for the evaluation of inhibitory activities against SecA ATPase.

Disclosure statement

The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

Additional information

Funding

This research was supported financially by the Natural Science Foundation of Hebei Province [B2019204032] and the Scientific Research Project of Hebei Agricultural University for Self-trained Talents [PY201812].