Sustainable Synthesis of Novel Tris-thio/Semicarbazones and Tris-rhodanines with Antiproliferative and Wastewater Treatment Applications

A new series of tris-rhodanines (3) and tris-thio/semicarbazones (5) have been designed, sono-synthesized, and characterized employing diverse spectral methods. Additionally, the copper complex (6) derived from the tris-thiosemicarbazone ligand (5b) successfully photodegraded methylene blue (MB) and showed superior effectiveness (97%), suggesting its potential for utilization in wastewater treatment systems. Furthermore, the antiproliferative activities of the designed compounds have been evaluated regarding MCF-7, A549 (cancer cell lines), and MCF-10A (normal cell lines). The results indicated that the developed compounds demonstrated promising inhibitory impacts (IC50 = 1.27–11.57 µM), even outperforming doxorubicin in certain cases. The copper complex (6) exhibited noteworthy anticancer properties (IC50 <1.30 µM) and a less cytotoxic influence on normal cell line (IC50 = 85.07 µM), suggesting potential as a leading candidate for cancer-preventing medicaments. The structure-activity relationship assessment revealed that hydrogen donor motifs, like carboxyl linked to rhodanine or terminal benzyl moiety connected to tris-thiosemicarbazones, are more effective in anticancer activities. Furthermore, density functional theory (DFT)-based quantum chemical analysis of the assembled molecules has been evaluated and found to be in agreement with the in vitro inhibiting activity. Lastly, the docking evaluation demonstrated that all of the designed compounds efficiently interacted with the targeted proteins' active sites (4AOR and 6JZ0) and had low binding energies, particularly compounds 5c (−8.35, −7.64 kcal/mol) and 6 (−7.59, −7.03 kcal/mol).