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Current Organocatalysis

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ISSN (Print): 2213-3372
ISSN (Online): 2213-3380

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Research Article

Synthesis and Characterization of Thioamidoalkyl Fluorescein Analogs for Antibacterial Activity and Molecular Docking Analyses

Author(s): Shazia Kousar*, Maryam Tabassum, Saif Mabkhot Qaid, Nur Intan Saidaah Mohamed Yusof, Fazlin Mohd Fauzi, Syed Adnan Ali Shah*, Muhammad Shahid, Madiha Irfan, Ayesha Monawar, Syed Waqas Bukhari and Muhammad Ahmad Mudassir*

Volume 12, Issue 3, 2025

Published on: 21 January, 2025

Page: [167 - 176] Pages: 10

DOI: 10.2174/0122133372319377241218122708

Price: $65

Abstract

Aims and Objectives: The study aimed to employ one-pot solvent-free boric acid-catalyzed multicomponent reactions (MCRs) to synthesize bioactive thioamidoalkyl fluorescein analogs. The study aimed to introduce a facile and environmentally sustainable strategy for efficiently producing alternate potent bioactivity agents.

Background: Population growth trends, limited efficacy and side effects of available medicine, and new challenges like antibiotic resistance have led to the urgent need for more and better pharmaceuticals and a notable increase in drug development. The global health demands and significant medicinal value of thioamidoalkyl compounds prompted synthesizing new fluorescein-based thioamidoalkyl derivatives to explore their prospective biomedical potential.

Methods: To prepare thioamidoalkyl fluorescein analogs, a solvent-free three-component reaction of fluorescein with aryl aldehydes and thiobenzamide catalyzed by boric acid was used. The antibacterial potentials of thioamidoalkyl fluorescein analogs against Escherichia coli (E. coli) bacteria were analyzed in terms of half-maximal inhibitory concentration (IC50). Moreover, molecular docking experiments explored the binding affinities and possible interaction mechanisms between newly synthesized analogs and active sites of E. coli adhesion protein FimH.

Results: FTIR, 1H, and 13C NMR results verified the successful formation of all analogs. The experimental and theoretical antibacterial activity results confirmed that the compound M-11 is relatively more potent against E. coli based on lower IC50 values of 54.14 nM and binding energy value of ‒6.30 kcal/mol (comparable to ‒6.70 kcal/mol of reference ligand) probably because of unique structure and strong binding affinities for target protein structure.

Conclusion: The findings demonstrated the potential of the currently employed synthetic approach to produce new analogs with decent yields facilely. Interestingly, the M-11 compound proved to be an excellent prospective source of antibiotic drugs based on both experimental and computational analyses.

Keywords: Multicomponent reactions, one-pot synthesis, thioamidoalkyl, aromatic aldehydes, antibacterial activity, fluorescein analogs, molecular docking.

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