Synthesis, in vitro α-amylase inhibitory, and radicals (DPPH & ABTS) scavenging potentials of new N-sulfonohydrazide substituted indazoles

Rafaila Rafique; Khalid Mohammed Khan; Arshia; Sridevi Chigurupati; Abdul Wadood; Ashfaq Ur Rehman; Uzma Salar; Vijayan Venugopal; Shahbaz Shamim; Muhammad Taha; Shahnaz Perveen

doi:10.1016/j.bioorg.2019.103410

Synthesis, in vitro α-amylase inhibitory, and radicals (DPPH & ABTS) scavenging potentials of new N-sulfonohydrazide substituted indazoles

Bioorg Chem. 2020 Jan:94:103410. doi: 10.1016/j.bioorg.2019.103410. Epub 2019 Oct 31.

Authors

Affiliations

¹ H.E.J. Research Institute of Chemistry, International Center for Chemical and Biological, Sciences, University of Karachi, Karachi 75270, Pakistan.
² H.E.J. Research Institute of Chemistry, International Center for Chemical and Biological, Sciences, University of Karachi, Karachi 75270, Pakistan; Department of Clinical Pharmacy, Institute for Research and Medical Consultations (IRMC), Imam Abdulrahman Bin Faisal University, P.O. Box 31441, Dammam, Saudi Arabia. Electronic address: khalid.khan@iccs.edu.
³ Department of Medicinal Chemistry and Pharmacognosy, Faculty of Pharmacy, Qassim University, Buraidah 52571, Saudi Arabia.
⁴ Department of Biochemistry, Shankar Campus, Abdul Wali Khan University, Mardan, Khyber Pukhtoonkhwa, Pakistan.
⁵ Dr. Panjwani Center for Molecular Medicine and Drug Research, International Center for Chemical and Biological Sciences, University of Karachi, Karachi 75270, Pakistan.
⁶ Faculty of Pharmacy, AIMST University, Kedah 08100, Malaysia.
⁷ Department of Clinical Pharmacy, Institute for Research and Medical Consultations (IRMC), Imam Abdulrahman Bin Faisal University, P.O. Box 31441, Dammam, Saudi Arabia.
⁸ PCSIR Laboratories Complex, Karachi, Shahrah-e-Dr. Salimuzzaman Siddiqui, Karachi 75280, Pakistan.

PMID: 31732193
DOI: 10.1016/j.bioorg.2019.103410

Abstract

Over-expression of α-amylase enzyme causes hyperglycemia which lead to many physiological complications including oxidative stress, one of the most commonly associated problem with diabetes mellitus. Marketed α-amylase inhibitors such as acarbose, voglibose, and miglitol used to treat type-II diabetes mellitus, but also linked to several harmful effects. Therefore, it is essential to explore new and nontoxic antidiabetic agents with additional antioxidant properties. In this connection, a series of new N-sulfonohydrazide substituted indazoles 1-19 were synthesized by multistep reaction scheme and assessed for in vitro α-amylase inhibitory and radical (DPPH and ABTS) scavenging properties. All compounds were fully characterized by different spectroscopic techniques including ¹H, ¹³C NMR, EI-MS, HREI-MS, ESI-MS, and HRESI-MS. Compounds showed promising α-amylase inhibitory activities (IC₅₀ = 1.23 ± 0.06-4.5 ± 0.03 µM) as compared to the standard acarbose (IC₅₀ 1.20 ± 0.09 µM). In addition to that all derivatives were found good to moderate scavengers of DPPH (IC₅₀ 2.01 ± 0.13-5.3 ± 0.11) and ABTS (IC₅₀ = 2.34 ± 0.07-5.5 ± 0.07 µM) radicals, in comparison with standard ascorbic acid having scavenging activities with IC₅₀ = 1.99 ± 0.09 µM, and IC₅₀ 2.03 ± 0.11 µM for DPPH and ABTS radicals. In silico molecular docking study was conducted to rationalize the binding interaction of α-amylase enzyme with ligands. Compounds were observed as mixed type inhibitors in enzyme kinetic characterization.

Keywords: ABTS and DPPH; In silico; In vitro; Indazole; Sulfonohydrazide; α-amylase enzyme.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Humans
Indazoles / chemical synthesis*
Indazoles / chemistry*
Molecular Docking Simulation / methods*
Molecular Structure
alpha-Amylases / antagonists & inhibitors*

Substances

Indazoles
alpha-Amylases