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image of Thieno-quinoline Derivatives as Promising Antimicrobial Agents: In Vitro and In Silico Insights

Abstract

Introduction

The global rise in antimicrobial resistance demands innovative therapeutic approaches. This study investigates novel 2-Aryl-9-chloro-5,6,7,8-tetrahydrothieno[3,2-b]quinoline derivatives (2a-e) as potential dual-action agents, targeting both pathogenic microorganisms and the phospholipase C-γ (PLC-γ) signaling pathway implicated in inflammatory responses.

Methods

Five derivatives were synthesized through a single-step POCl3-catalyzed cyclocondensation of thiophene carboxylic acids with cyclohexanone, yielding 55-71% of purified products. Antimicrobial efficacy was evaluated against Gram-positive ( ATCC 25923, ATCC 10876), Gram-negative ( ATCC 25922, clinical isolate), and ATCC 10231 strains using standardized CLSI protocols. Computational studies employed molecular docking (MolDock) and binding free energy calculations against PLC-γ (PDB ID:5EG3).

Results

Among the tested compounds, compounds 2-c and 2-e showed strong antibacterial activity against , even surpassing gentamicin. Compounds 2-b and 2-d, on the other hand, showed significant antifungal activity against Candida albicans, equivalent to that of DEPTIL BFC. Molecular docking revealed compound 2d (L) as the most potent PLC-γ inhibitor (ΔG=-116.127 kcal/mol), forming π-alkyl interactions with Ala 567 in the catalytic pocket.

Discussion

The structure-activity relationship demonstrates that chloro-substitution at position 9 enhances antimicrobial potency, while aryl modifications at position 2 influence PLC-γ binding affinity. These findings suggest a unique dual mechanism of action distinct from conventional antimicrobials.

Conclusion

his study highlights the biological potential of [Aryl-CTTQ] derivatives (2a-e), in particular their marked antibacterial activity and, for some, moderate antifungal activity. Compound 2d (L) is distinguished by its high affinity for phospholipase C-γ, identified through and analyses. These results validate the effectiveness of a computer-aided design approach to develop new therapeutic agents.

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2025-10-21
2025-12-16

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Thieno-quinoline Derivatives as Promising Antimicrobial Agents: In Vitro and In Silico Insights
Bentham Science Publishers ; https://doi.org/10.2174/0122127968408290251007135735
/content/journals/ccb/10.2174/0122127968408290251007135735
/content/journals/ccb/10.2174/0122127968408290251007135735
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  • Article Type:     Research Article
Keywords: Computational chemistry ; antifungal activity ; phospholipase C-γ ; thieno-quinoline derivatives ; antibacterial activity ; molecular docking

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