Synthesis, Characterization, In Vitro Anticancer Activity, In Silico ADMET Profiling, and Molecular Docking Studies...

In line with the need for new candidate molecules in cancer treatment, 2-substituted benzothiazole derivatives were synthesized in this study, their antiproliferative activities were evaluated, and their potential was investigated through ADMET, DFT, and molecular docking studies. During the synthesis process, 7-arylidinobicyclo[3.2.0]heptan-6-one intermediates were reacted with 2-amino-benzenethiol in the presence of p-toluenesulfonic acid under reflux conditions to obtain the target 2-((1S,2S)-2-((E)-substituestyryl)cyclopentyl)benzo[d]thiazole derivatives. The structures were confirmed by NMR and IR spectroscopy. The antiproliferative effects of the compounds were evaluated using the BrdU test in C6 and HeLa cell lines. In the cytotoxicity test, compounds 16 and 20 showed the highest cytotoxicity against C6 cells (IC₅₀: 28.68 and 26.39 µM). Against HeLa cells, compounds 14, 16, and 19 showed notable activity (IC₅₀: < 5, 22.83, and 15.82 µM, respectively). DFT calculations (B3LYP/6-31G+(d,p)) showed strong agreement with experimental NMR data. MEP maps were generated for compounds 14-20, and potential regions contributing to biological activity were analyzed. ADMET analysis indicated that the compounds have suitable pharmacokinetic and oral bioavailability profiles. Molecular docking showed that compound 17 has strong interactions with the target proteins (PDB: 1M17 for HeLa and PDB: 1JQH for C6). In conclusion, compounds 14-20 emerge as potential candidates in anticancer drug development processes.