ISSN print edition: 0366-6352 ISSN electronic edition: 1336-9075 Registr. No.: MK SR 9/7 Published monthly

New arylidene-linked chromane-2,4-dione analogs as potential leads for diabetic management; syntheses, α-amylase inhibitory, and radical scavenging activities

Israr ul Haq, Irfan Ali, Khalid Mohammed Khan, Sridevi Chigurupati, Atiya Habib, Uzma Salar, Manzoor Ahmad, Sreenath Konanki, Shatha Ghazi Felemban, Muhammad Taha, and Zaheer Ul Haq

International Center for Chemical and Biological Sciences, H. E. J. Research Institute of Chemistry, University of Karachi, Karachi, Pakistan

E-mail: khalid.khan@iccs.edu

Received: 24 March 2022  Accepted: 25 December 2022

Abstract:

A range of substituted arylidene chromane-2,4-dione derivatives 1–30 were synthesized by the condensation reaction between 6-chloro-4-hydroxycoumarin and different benzaldehydes in ethanol. All synthesized derivatives are structurally new and fully characterized by various spectroscopic approaches. Compounds were tested for α-amylase inhibitory and radical (DPPH and ABTS) scavenging activities in vitro. When compared to the standard acarbose (IC₅₀ = 12.9 ± 0.1 µM), all derivatives showed significant inhibitory activity against the α-amylase enzyme, with IC₅₀ values ranging from 7.7 ± 0.1 to 60.7 ± 0.1 µM. Compounds were also found to be good radical scavengers of DPPH (IC₅₀ = 21.6 ± 0.2 to 92.1 ± 0.1 µM) and ABTS (IC₅₀ = 22.4 ± 0.1 to 92.7 ± 0.1 µM), compared to standard ascorbic acid (DPPH, IC₅₀ = 14.4 ± 0.1; ABTS, IC₅₀ = 14.9 ± 0.1 µM). Kinetic studies performed on most active molecules revealed competitive-type inhibition mechanisms. The structure–activity relationship (SAR) has been studied to determine the effect of different substitutions of compounds on inhibitory potential. Docking studies of these synthesized coumarin derivatives revealed significant binding interactions with the α-amylase enzyme's catalytic site.

Keywords: Coumarin; α-Amylase inhibitors; Kinetics; Docking studies; Radical scavengers

Full paper is available at www.springerlink.com.

DOI: 10.1007/s11696-022-02648-5

Chemical Papers 77 (5) 2581–2604 (2023)