AUTHOR=Ahmed Atteeque , Zaib Sumera , Bhat Mashooq Ahmad , Saeed Aamer , Altaf Muhammad Zain , Zahra Fatima Tuz , Shabir Ghulam , Rana Nehal , Khan Imtiaz 

TITLE=Acyl pyrazole sulfonamides as new antidiabetic agents: synthesis, glucosidase inhibition studies, and molecular docking analysis

JOURNAL=Frontiers in Chemistry

VOLUME=12

YEAR=2024

URL=https://www.frontiersin.org/journals/chemistry/articles/10.3389/fchem.2024.1380523

DOI=10.3389/fchem.2024.1380523

ISSN=2296-2646

ABSTRACT=<p>Diabetes mellitus is a multi-systematic chronic metabolic disorder and life-threatening disease resulting from impaired glucose homeostasis. The inhibition of glucosidase, particularly <italic>α</italic>-glucosidase, could serve as an effective methodology in treating diabetes. Attributed to the catalytic function of glucosidase, the present research focuses on the synthesis of sulfonamide-based acyl pyrazoles <bold>(5a-k)</bold> followed by their <italic>in vitro</italic> and <italic>in silico</italic> screening against <italic>α</italic>-glucosidase. The envisaged structures of prepared compounds were confirmed through NMR and FTIR spectroscopy and mass spectrometry. All compounds were found to be more potent against <italic>α</italic>-glucosidase than the standard drug, acarbose (IC<sub>50</sub> = 35.1 ± 0.14 <italic>µ</italic>M), with IC<sub>50</sub> values ranging from 1.13 to 28.27 <italic>µ</italic>M. However, compound <bold>5a</bold> displayed the highest anti-diabetic activity (IC<sub>50</sub> = 1.13 ± 0.06 <italic>µ</italic>M). Furthermore, <italic>in silico</italic> studies revealed the intermolecular interactions of most potent compounds (<bold>5a</bold> and <bold>5b</bold>), with active site residues reflecting the importance of pyrazole and sulfonamide moieties. This interaction pattern clearly manifests various structure–activity relationships, while the docking results correspond to the IC<sub>50</sub> values of tested compounds. Hence, recent investigation reveals the medicinal significance of sulfonamide-clubbed pyrazole derivatives as prospective therapeutic candidates for treating type 2 diabetes mellitus (T2DM).</p>