Novel C-4 sulfenylated pyrazoles as α-amylase inhibitors: Insights from in silico and in vitro studies.

Diabetes rank among the most critical health challenges globally. Consequently, the development of therapeutic agents targeting this health issue has become a focal point for researchers worldwide. To achieve this, tetra substituted pyrazoles were synthesized in two steps: initially, thiolated diketones were prepared using NaOH/KI catalysed approach in acetonitrile. Afterwards, the desired pyrazole analogues were achieved by condensation of thiolated 1,3-diketone and benzenesulfonamide hydrazine in refluxing ethanol. All derivatives were synthesized with moderate to high efficiency. After successfully establishing their molecular structure, the inhibitory potential of derived synthetics was subsequently assessed using in vitro α-amylase assay. All the synthesized derivatives demonstrated good inhibitory activity against α-amylase. Among all, compound 6b and 6i displayed highest inhibition of α-amylase with lower IC50 values than acarbose. After establishing the inhibitory potential of pyrazole analogues against α-amylase, both compound 6b and 6i were screened for their α-glycosidase inhibition properties. Kinetic experiments revealed that the compound 6b and 6i exhibited a mixed mode of α-amylase as well as α-glycosidase inhibition. The significant inhibition of the selected enzymes by chloro substituted analogues certainly shows relevance of "magic chloro effect" in biological system. The experimentally determined biological results strongly corroborated the in silico findings.