Thiazole Derivatives as RORt Inhibitors: Synthesis, Biological Evaluation, and Docking Analysis

Background Cancer is a serious concern in developing countries. Due to various worldwide impacts, it has surpassed coronary disorders becoming the leading cause of mortality. In cancer progression, the involvement of RORs (retinoic acid receptor-related orphan receptors) has gained attention in the search for versatile agents. Thiazole has the potential to be used as a scaffold in the development of anticancer drugs. Objective This work's major goal was to design and synthesize promising anticancer candidates. Methods Docking investigations concerning the ROR gamma t receptor were utilized in the design of the compounds. A series of novel thiazole derivatives was synthesized employing Hantsch synthesis. Melting points, TLC development, and spectral analyses were considered for the synthesized compounds' characterization. Corresponding spectra were analyzed and determined to be consistent with the assigned structure. On 60 human cancer cell lines, selected compounds were investigated in vitro by NCI (National Cancer Institute), USA, for anticancer action. Results Varying ratios of anticancer potential were presented by the compounds in in vitro studies. Compound 3c was determined to be the most active compound in the series, with a -15.03 mean growth percent. In silico study revealed that the synthesized compounds could have anticancer possibilities. In the targeted pdb id (6q7a) binding site, compound 3c demonstrated excellent docking scores in molecular docking analyses, supporting its ability to be utilized as a lead compound in rational drug design. Conclusion Compounds with satisfactory docking scores within the binding pocket of chosen pdb id (6q7a) validated their suitability for usage as lead compounds in rational drug design. Outcomes of in silico investigations were in agreement with the findings of the cytotoxicity experiments. Leukemia, renal, breast, and lung cancer cell lines were most sensitive to the substance-treated tumor cells. Electron-withdrawing groups were essential for antiproliferative action, according to the findings.