Synthesis of Novel Dioxathiole-6,7-coumarin Hybrids As Cytosafe-Multifunctional Applicants: An In Vitro—In Silico Study

Objective: This work reported for the first time the synthesis of novel hybrids described as a five-membered ring with three heteroatoms fused on the 6,7-coumarin framework. This is an endeavor to discover adaptable and easily obtainable coumarin frameworks possessing a wide array of biomedical characteristics. Methods: Seven hybrids constructed from 1,3,2-dioxathiole-2-oxide and coumarin derivatives were fabricated through a three-step synthetic process originating from benzene 1,2,4-triole. Spectroscopic methodologies, encompassing 1H, 13C NMR, and FT-IR, were utilized to validate the structural framework of the synthesized hybrids. Their potential in the biomedical realm to function as antitumor agents, suppressors of inflammation, oxidative stress alleviators, and regulators of blood sugar levels was assessed. In addition, their cytosafety and in silico pharmacokinetic parameters were also investigated. Six cancerous cell lines were utilized to investigate the antitumor activity of the synthesized hybrids through the MTT-dependent assay, while three noncancerous cell lines were employed to examine the compounds’ cytocsafety. The inflammatory suppressant potential was investigated against three inflammatory-related enzymes. The antioxidant activity was investigated in oxidative stress-induced human cells, while the antidiabetic potential was investigated through two carbohydrate-digesting enzymes. Finally, two web-based programs were utilized to reveal the pharmacokinetic profiles of the title hybrids. Results and Discussion: Four principal outcomes were reported based on the extracted findings. The dioxathiole-coumarin hybrids have encouraging and extensive biomedical impacts. Hybrid (DOT3) had potent antitumor, antioxidant, and cytosafety potentials. Compound (Precursor O-III) exhibited potent anti-inflammatory potential through the lipoxygenase-dependent pathway (IC50 = 9.22 ± 1.02 µg/mL). Compounds (DOT1) and (DOT2) have significant potential as antidiabetic agents, as evidenced by their potent inhibition capacities toward glucosidase and amylase. Conclusions: Compounds (DOT3), (Precursor O-III), (DOT1), and (DOT2) exhibited the potential to function as valuable scaffolds for screening novel medications with antitumor, antioxidant, anti-inflammatory, and antidiabetic properties in the foreseeable future.