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New 1, 2, 4‐oxadiazole/pyrrolidine hybrids as topoisomerase IV and DNA gyrase inhibitors with promising antibacterial activity

Research Authors
Firas OA Frejat, Yaquan Cao, Lihong Wang, Hongjin Zhai, Ahmed H Abdelazeem, Hesham AM Gomaa, Bahaa GM Youssif, Chunli Wu
Research Date
Research Journal
Archiv der Pharmazie
Research Year
2022
Research_Pages
e2100516
Research Abstract

 

A series of hybridized pyrrolidine compounds with a 1,2,4‐oxadiazole moiety were synthesized to develop effective molecules against the enzymes DNA gyrase and topoisomerase IV (Topo IV). Compounds 8–20 were developed based on a previously disclosed series of compounds from our lab, but with small structural modifications in the hopes of increasing the compounds' biological activity. In comparison to novobiocin, with IC50 = 170 nM, the findings of the DNA gyrase inhibitory assay revealed that compounds 16 and 17 were the most potent of all synthesized derivatives, with IC50 values of 180 and 210 nM, respectively. Compound 17 had the strongest inhibitory effect against Escherichia coli Topo IV of all the synthesized compounds, with an IC50 value of 13 µM, which was comparable to novobiocin (IC50 = 11 µM). Therefore, hybrids 16 and 17 appeared to be potential dual‐target inhibitors. In the …