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

Design, synthesis and biological evaluation of novel phthalimide-Schiff base-coumarin hybrids as potent α-glucosidase inhibitors

Maedeh Sherafati, Maryam Mohammadi-Khanaposhtani, Shahram Moradi, Mohammad Sadegh Asgari, Nadia Najafabadipour, Mohammad Ali Faramarzi, Mohammad Mahdavi, Mahmood Biglar, Bagher Larijani, Haleh Hamedifar, and Mir Hamed Hajimiri

Department of Chemistry, Tehran North Branch, Islamic Azad University, Tehran, Iran

E-mail: momahdavi@tums.ac.ir

Received: 1 February 2020  Accepted: 7 June 2020

Abstract:

We have designed and synthesized phthalimide-Schiff base-coumarin hybrids 8a–b, 9a–d, 10a–b, and 11a–d and evaluated them for α-glucosidase inhibitory potential against yeast form of this enzyme. For the synthesis of title compounds 4-hydroxybenzaldehyde, 4-hydroxy-3-methoxybenzaldehyde, 2-hydroxybenzaldehyde, 2-hydroxybenzaldehyde derivatives, coumarin-3-carbohydrazide, and coumarin-7-yloxy-acetohydrazide were used. In vitro α-glucosidase inhibition revealed that all the synthesized compounds exhibited outstanding α-glucosidase inhibition with IC₅₀ values ranging between 85.2 ± 1.7 and 577.7 ± 7.5 µM when compared with the standard inhibitor acarbose having IC₅₀ value 750.0 ± 12.0 µM. The most potent compounds were 4-hydroxybenzaldehyde derivative 8a with coumarin-3-carbohydrazide moiety, 2-hydroxy-5-nitrobenzaldehyde derivative 11d with coumarin-7-yloxy-acetohydrazide moiety, and 2-hydroxy-5-nitrobenzaldehyde derivative 9d with coumarin-3-carbohydrazide moiety. Molecular docking studies were carried out to understand the interaction modes and binding energies of the most active compounds and standard drug acarbose. This studies predicted that compounds 8a, 11d, and 9d (respectively with binding energies = − 10.77, − 8.65, and − 8.66 kcal/mol) bind to active site α-glucosidase more easily than acarbose (binding energy = − 4.04 kcal/mol).

Keywords: α-Glucosidase; Docking study; Kinetic study; Phthalimide; Schiff base; Coumarin

Full paper is available at www.springerlink.com.

DOI: 10.1007/s11696-020-01246-7

Chemical Papers 74 (12) 4379–4388 (2020)