Design, synthesis, in-silico and biological evaluation of novel 2-Amino-1,3,4-thiadiazole based hydrides as B-cell lymphoma-2 inhibitors with potential anticancer effects

In the current study, 5-(pyridin-2-yl)-1,3,4-thiadiazol-2-amine (1) was synthesized via one step reaction of picolinic acid with thiosemicarbazide in the presence of POCl3 Then it's used as a key synthon in a two-component one-pot synthesis of novel fused heterocyclic moieties as imidazo[2,1-b]-thiadiazoles 2a-c , thiadiazolo[3,2-a]pyrimidines 3-8 derivatives containing new fused ring pyrimidines or imidazoles. In addition to traditional heating, the compounds were synthesized using microwave irradiation as an environmentally friendly method. Physical, spectroscopic, and analytical data were used to characterize all of the newly synthesized compounds. These novel compounds were examined for their antioxidant efficacy and screened in-silico for their ability to inhibit cancer proliferation by inducing intrinsic mito-chondrial membrane dysfunction, which is an effective strategy for cancer cell death. Compound 2c ex-hibited the highest antioxidant scavenging activity using 2,2-diphenyl-1-picryhydrazyl and 2,2'-azino-bis (3-ethylbenzothiazoline-6-sulfonic acid) radicals. As well, compound 2c achieved the best results, afford-ing the highest binding energy of-10.06 kcal/mol for the target antiapoptotic B-cell lymphoma-2 (Bcl-(2)) protein; thus, it was selected for the in-vitro anticancer effect against Caco, PCL, MCF-7, and MDA-231 cancer cell lines. The in-vitro studies were found to be in line with molecular docking simulations. These results demonstrate the potential of compound 2c as a drug candidate for cancer therapy. (C) 2022 Published by Elsevier B.V.

Automated summary

In this study, a one-step reaction was used to synthesize 5-(pyridin-2-yl)-1,3,4-thiadiazol-2-amine, which was then used as a key synthon in the synthesis of novel fused heterocyclic compounds. These compounds exhibited antioxidant activity and potential as anticancer drugs.