Synthesis, biological and computational analysis of indazole derivatives as alpha-glucosidase and alpha-amylase agents

Indazole analogues (1–14) were synthesized, elucidated their structure by using various spectroscopic techniques like ¹HNMR, ¹³CNMR and HREI-MS and evaluated against α-glucosidase and α-amylase enzymes. All derivatives demonstrated better α-glucosidase and α-amylase inhibitory potential with IC₅₀ value ranging from 9.80 ± 0.60 to 47.20 ± 0.10 µM (against α-glucosidase) and 4.70 ± 0.40 to 4.70 ± 0.40 µM (against α-amylase) as compared with the standard drug acarbose (IC₅₀ = 38.45 ± 0.80 & 11.12 ± 0.15 µM, respectively).

In case of α-glucosidase analogues 7 (IC₅₀ = 9.80 ± 0.60 µM), while in case α-amylase analogue 1 (IC₅₀ = 14.70 ± 0.40µM) show most potent inhibitory potential. Furthermore, molecular docking studies were carried out for the binding interaction of the most potent molecule-7, with the enzyme’s active site is primarily influenced by the presence of the di‑chloro group. This group enhances the electron-withdrawing (EW) effect on the aromatic ring, which strengthens hydrophobic interactions in the case of glucosidase inhibition. On the other hand, molecule-1, which contains an electron-donating group (EDG), increases the overall electronic density, thereby facilitating stronger interactions with the enzyme’s active site in the case of amylase inhibition.