Novel oxadiazole-thiadiazole derivatives: synthesis, biological evaluation, and in silicostudies

AbstractIn the search for new anticancer agents, we synthesized a new series of thiazole derivatives carried on thiadiazole-oxadiazole hybrid. Final compounds (5a–5i) were analyzed via1H NMR, 13C NMR, and HRMS. The pharmacokinetic profile of the targeted compounds was predicted via in silicocalculations. Their anticancer properties were determined using MTT method against MCF7 and A549 cell lines. Compounds 5a, 5band 5cwere found more active against MCF7 cells than A549 cells while they were not cytotoxic on L929 healthy cells. Generally, it can be summarized that acetamide moiety has a pivotal role in anticancer activity. For further studies, their aromatase inhibitory activity was evaluated. After determination all these features, the binding modes of the active compounds and the stability and relation of the ligand-enzyme complex were investigated using molecular docking and molecular dynamics simulation studies, respectively. In vitroand in silicostudies suggest two important structure-activity relationship (SAR) points that at least one azole ring is essential, and if there is approximately 8.0 ± 0.5 Å distance between the H-bond rich zone of ligand and the heteroaryl ring system of ligand has a major impact on aromatase inhibitory activity. Compounds with small group substitution on thiazole are found potentially may be used for the treatment of anti-breast cancer orally.Communicated by Ramaswamy H. Sarma