Evaluation of Novel Carbazolyl Thiourea and Carbazolyl Thiazolidinone Derivatives against Human Bladder Tumor Cell Lines: Synthesis, Apoptosis, Cell Cycles, Molecular Docking, and In Silico ADMET Prediction Studies

A series of novel thiourea and thiazolidinone derivatives linked to a carbazole ring (2a–2e and 3a–3e) at the C-3 position were efficiently synthesized using ultrasound irradiation. All synthesized compounds were evaluated for their in vitro cytotoxicity against HT1376 and T24 which are both human bladder cancer cell lines. Many of the tested compounds showed significant cytotoxic properties. Compounds 2c and 3b showed the highest cytotoxicity, even more so than doxorubicin, a common chemotherapy drug used as a reference point. Furthermore, these two compounds significantly induced late apoptosis and necrosis in the studied tumor cells. Additionally, both compounds 2c and 3b demonstrated a promising ability to arrest the cell cycle at distinct phases in both HT1376 and T24 cells. Consistent with the apoptosis data, compounds 2c and 3b displayed potential for autophagic induction. The ADMET prediction suggested that both bioactive products may be effective anticancer treatments. The identified compounds also exhibited strong binding interactions during molecular docking investigations with the VEGFR-2 receptor. These findings suggested that compounds 2c and 3b possess a valuable skeletal structure for the development of novel antitumor agents.