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

Synthesis, molecular structure characterization, and in vitro and in silico investigations of heterocyclic N-butylamide-substituted carboxamides

R. Kavitha, M. P. Ramya Rajan, S. Sivagami, R. Nithya Balaji, and K. Jayamoorthy

Department of Physics, Rajalakshmi Institute of Technology, Chennai, India

E-mail: kjmche@gmail.com

Received: 8 March 2025  Accepted: 8 July 2025

Abstract:

Small-molecule drugs have garnered significant attention due to their diverse pharmacological applications. Heterocyclic rings play a pivotal role in drug design and discovery, while amide functional groups are essential for biological activity. In this study, we synthesized a series of amides incorporating various heterocyclic units, including phenyl, quinoline, pyridyl, indole, and thiophene. The structural integrity of the synthesized compounds was confirmed through comprehensive analytical techniques. Their anti-diabetic and anti-inflammatory activities were evaluated in vitro, with molecular docking studies further supporting their potential interactions with key enzymes involved in diabetes and inflammation. Additionally, theoretical investigations, including DFT calculations, molecular electrostatic potential mapping, and Mulliken charge distribution analysis, provided insights into the electronic properties and reactivity of the compounds. Among the synthesized compounds, INNBA exhibited the highest in vitro anti-inflammatory and α-amylase inhibition, reaching 97.0% and 94.5%, respectively. Docking studies revealed strong binding affinities, with binding energies up to − 6.63 kcal/mol (4-COX, INNBA). DFT analysis showed HOMO–LUMO band gaps ranging from 4.33 (QUNBA) to 5.74 eV (PHNBA), supporting the observed reactivity trends. These findings highlight the potential of heterocyclic amide derivatives as promising candidates for further pharmacological exploration.

Graphical abstract

Keywords: Heterocyclic; Small compounds; Molecular docking; DFT; In vitro and in silico

Full paper is available at www.springerlink.com.

DOI: 10.1007/s11696-025-04239-6

Chemical Papers 79 (11) 7383–7399 (2025)