Synthesis, α-amylase and α-glucosidase inhibition and molecular docking studies of indazole derivatives

Abstract

Herein, we report the synthesis and inhibitory potential of indazole (Methyl 1H-indazole-4-carboxylate) derivatives (1–13) against α-amylase and α-glucosidase enzymes. The described derivatives demonstrated good inhibitory potential with IC₅₀ values, ranging between 15.04 ± 0.05 to 76.70 ± 0.06 µM ± SEM for α-amylase and 16.99 ± 0.19 to 77.97 ± 0.19 µM ± SEM for α-glucosidase, respectively. In particular, compounds (8–10 and 12) displayed significant inhibitory activities against both the screened enzymes, with their inhibitory potential comparable to the standard acarbose (12.98 ± 0.03 and 12.79 ± 0.17 µM ± SEM, respectively). Additionally, the influence of different substituents on enzyme inhibition activities was assessed to study the structure activity relationships. Molecular docking simulations were performed to rationalize the binding of derivatives/compounds with enzymes. All the synthesized derivatives (1–13) were characterized with the aid of spectroscopic instruments such as ¹H-NMR, ¹³C-NMR, HR-MS, elemental analysis and FTIR.

Communicated by Ramaswamy H. Sarma

Keywords:

• Indazole
• α-amylase activity
• α-glucosidase activity
• molecular docking
• spectral studies
• NMR
• HR-MS
• FTIR

Disclosure statement

No potential conflict of interest was reported by the authors.

Additional information

Funding

This work was funded by Imam Abdulrahman Bin Faisal University (IAU) (project number: 2019-126-DSR). Authors would like to express their gratitude towards the Institute for Research and Medical Consultations (IRMC) at IAU for the laboratory support.