https://doi.org/10.1140/epjs/s11734-026-02238-6
Regular Article
Computational and experimental insights into the sustainable synthesis and physicochemical interactions of N-substituted chromene–sulfonamide derivatives
1
Department of Chemistry, School of Applied and Life Sciences, Uttaranchal Institute of Technology, Uttaranchal University, 248007, Dehradun, Uttarakhand, India
2
Department of Pharmaceutical Chemistry, School of Pharmaceutical Sciences, Shri Guru Ram Rai University, 248001, Dehradun, Uttarakhand, India
3
Department of Chemistry, A N College, Patliputra University, 800013, Patna, Bihar, India
4
Department of Biochemistry, Giri Diagnostic Kits and Reagents Pvt. Ltd., F-105 Industrial Area, Selaqui, 248011, Dehradun, Uttarakhand, India
5
Department of Biology, Faculty of Science, Jazan University, 45142, Jazan, Saudi Arabia
6
Department of Physical Sciences, Chemistry Division, College of Science, Jazan University, P.O. Box 114, 45142, Jazan, Kingdom of Saudi Arabia
7
Engineering and Technology Research Center, Jazan University, P.O. Box 114, 45142, Jazan, Saudi Arabia
8
Department of Chemical Engineering Technology, College of Applied Industrial Technology, Jazan University, 45142, Jazan, Saudi Arabia
a
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b
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Received:
4
November
2025
Accepted:
23
February
2026
Published online:
5
March
2026
Abstract
Chromene–sulfonamide derivatives have attracted significant interest for their promising antimicrobial properties. In this study, a series of N-substituted chromene–aryl sulfonamides were synthesized using a green and efficient two-step protocol. In the first step, multifunctional amino chromenes were obtained via a one-pot, three-component reaction under solvent-minimized conditions. This reaction involved substrates containing –OH, –CHO, and –CN groups, catalyzed by l-proline, a biodegradable and non-toxic organocatalyst. In the second step, the amino chromenes were converted to sulfonamide derivatives by reaction with p-toluenesulfonyl chloride using pyridine as both catalyst and solvent. The synthesized compounds were evaluated for antibacterial activity against Escherichia coli, Salmonella typhimurium, and Staphylococcus aureus. Several derivatives exhibited notable antibacterial potency, particularly against both Gram-negative and Gram-positive strains. Structure–activity relationship analysis revealed that electron-donating and -withdrawing substituents on the aryl aldehyde ring significantly influenced biological activity. Molecular docking studies further supported the experimental results, demonstrating strong binding affinities of key compounds with bacterial targets. Among them, CS6 and CS10 showed the highest binding energies, with ΔG values ranging from − 7.56 to − 40.56 kcal/mol. This work highlights an environmentally benign synthetic approach for producing bioactive chromene-based sulfonamide derivatives. The combination of green chemistry and pharmacological relevance suggests potential applications in antimicrobial drug development.
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© The Author(s), under exclusive licence to EDP Sciences, Springer-Verlag GmbH Germany, part of Springer Nature 2026
Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.
