A new synthetic approach for determination of thiadiazole clubbed sulfonamide as diabetic therapeutic with in silico modeling and kinetic study
Year: 2025
Type: article
Abstract: Diabetes mellitus (DM), an endocrine disorder characterized by impaired glucose secretion leading to hyperglycemia, was targeted in the current research study. Pursuant to this investigative strategy, we have synthesized, characterized and analyzed a series of new thiadiazole based sulfonamide derivatives with significant potential against diabetes mellitus. This therapeutic breakthrough for DM was achieved via in vitro biomedical investigation of newly synthesized compounds as robust inhibitors of α-amylase and α-glucosidase enzymes. The substantial efficacy of the new lead compound of the series was due to presence of trifluoromethyl moiety substitution at para position of the phenyl ring awarding strong inhibition potential, IC 50 of 4.70 ± 0.30 and 5.70 ± 0.30 µM in comparison to reference drug acarbose (IC 50 =7.10 ± 0.20 µM and 8.30 ± 0.20 µM). The in vitro therapeutic effect was also validated via in silico studies. Enzyme kinetics of the lead compounds showed the dose-response potential showing its efficacy to inhibit the target enzymes. The interactions resulting in inhibition of both enzymes caused by the lead compounds were also visualized under molecular docking study for validation of biological activity. ADMET analysis of potent compounds presented the non-toxic nature and compels their use as future treatment. DFT studies also presented the charge distribution of the compounds which is responsible for chemical reactivity and interaction with the enzymes. The cumulative results from our comprehensive in vitro and in-silico investigations unequivocally demonstrate the therapeutic potential of the new potent compounds as efficacious agents for the mitigation and treatment of Diabetes mellitus (DM).
Source: Journal of Molecular Structure
Authors: Shoaib Khan, Tayyiaba Iqbal
Language: English
Subfield: Organic Chemistry
Field: Chemistry
Domain: Physical Sciences
Open Access status: hybrid
Estimated APC paid: $3,360
OpenAlex ID: W4409251079