An alternative technique for cyclization synthesis, in vitro anti-esophageal cancer evaluation, and molecular docking of novel thiazolidin-4-one derivatives

Abstract

In this work, two novel series of thiazolidin-4-one derivatives (9a–e and 10a–e) constituting ten compounds were synthesized under batch and ultrasound irradiation. It is found that the use of sonochemical methodology in the thiazolidin-4-ones synthesis offers several ecological advantages such as an effective, inexpensive, easy applicable, eco-friendly, and waste-free chemicals than the batch method. Different techniques including NMR (1H and 13C), mass spectra, and infrared radiation (FTIR) were employed to characterize the chemical structures of all the synthesized thiazolidin-4-one derivatives. The purified derivatives were tested for their anti-esophageal cancer activity against a panel of human esophageal cancer cell line (SKGT-4). The in vitro cytotoxic and apoptotic activities of these derivatives were evaluated by MTT and AO/EB assays, respectively. Among these derivatives, thiazolidin-4-one derivatives 9e and 10b were found to have the most potency toward SKGT-4 human esophageal cells. When compared to the reference standard (cisplatin, IC50 5.21±0.41 µg/mL), the values (IC50) of the derivatives 9e and 10b were found as 17.6 ± 0.06 and 18.5 ± 0.01 μg/mL, respectively. The collected data from AO/EB assay revealed these derivatives are able to stimulate the apoptotic effect in the SKGT-4 cells with a selective pathway compared to their behaviors in the normal Vero cells. Moreover, DFT-assisted calculations with theoretical level: B3LYP/6–31G(d,p) were adopted to optimize the geometrical structures of the derivatives 9e and 10b. To elucidate the possible binding mechanisms of these derivatives 9e and 10b with the active sites of human esophageal proteins (PDB ID: 6DUK, 2LEO, and 5HZN), the docking study was accomplished. According to the docking analysis, the derivatives 9e and 10b showed efficient interactions with the target receptors with low values of binding affinity. Thus, the biological tests and docking scores suggested that the synthesized thiazolidin-4-one derivatives 9e and 10b may be considered as a potential candidate for esophageal cancers treatments.