Head-to-head bisbenzazole derivatives as antiproliferative agents: design, synthesis, in vitro activity, and SAR analysis

Ersan, Ronak HajAlagoz, Mehmet AbdullahErtan-Bolelli, TugbaDuran, NizamiBurmaoglu, SerdarAlgul, Oztekin2024-09-182024-09-1820211381-19911573-501Xhttps://doi.org/10.1007/s11030-020-10115-0https://hdl.handle.net/20.500.12483/8228In the present work, a series of bisbenzazole derivatives were designed and synthesized as antiproliferative agents. The antiproliferative activity of these compounds was investigated using MTT assay. Bisbenzazole derivatives showed significant antiproliferative activity against all the four tested cancer cell lines. Among the various bisbenzazole derivatives, bisbenzoxazole derivatives exhibited the most promising anticancer activity followed by bisbenzimidazole and bisbenzothiazole derivatives. All the derivatives were found to be less toxic as compared to methotrexate (positive control) in normal human cells, indicating selective and efficient antiproliferative activity of these bisbenzazole derivatives. The structure-activity relationships of heteroaromatic systems and linkers present in bisbenzazole derivatives were analyzed in detail. In silico ADMET prediction revealed that bisbenzazole is a drug-like small molecule with a favorable safety profile. Compound31is a potential antiproliferative hit compound that exhibits unique cytotoxic activity distinct from methotrexate. [GRAPHICS]eninfo:eu-repo/semantics/closedAccessBisbenzimidazoleBisbenzoxazoleBisbenzothiazoleAntiproliferative activitySARADMETHead-to-head bisbenzazole derivatives as antiproliferative agents: design, synthesis, in vitro activity, and SAR analysisArticle2542247225910.1007/s11030-020-10115-0325568042-s2.0-85086647957Q1WOS:000541187100001Q2