Comprehensive Report
Natural Coumarin-Hybridized Thiazolylbenzonitriles as New Structural Scaffolds to Exert Potentially Multitargeting Supramolecular Antibacterial Behavior
Qian-Yue Li,
Chun-Mei Zeng,
Yao Chen,
Nisar Ahmad,
Shao-Lin Zhang,
Cheng-He Zhou,
Qian-Yue Li
Institute of Bioorganic & Medicinal Chemistry, Key Laboratory of Applied Chemistry of Chongqing Municipality, School of Chemistry and, Chemical Engineering, Southwest University, Chongqing, 400715 China
These authors contributed equally to this work.
Search for more papers by this authorChun-Mei Zeng
Institute of Bioorganic & Medicinal Chemistry, Key Laboratory of Applied Chemistry of Chongqing Municipality, School of Chemistry and, Chemical Engineering, Southwest University, Chongqing, 400715 China
These authors contributed equally to this work.
Search for more papers by this authorYao Chen
Institute of Bioorganic & Medicinal Chemistry, Key Laboratory of Applied Chemistry of Chongqing Municipality, School of Chemistry and, Chemical Engineering, Southwest University, Chongqing, 400715 China
These authors contributed equally to this work.
Search for more papers by this authorNisar Ahmad
Institute of Bioorganic & Medicinal Chemistry, Key Laboratory of Applied Chemistry of Chongqing Municipality, School of Chemistry and, Chemical Engineering, Southwest University, Chongqing, 400715 China
Search for more papers by this authorCorresponding Author
Shao-Lin Zhang
School of Pharmaceutical Sciences, Chongqing Key Laboratory of Natural Product Synthesis and Drug Research, Chongqing University, Chongqing, 401331 China
E-mail: [email protected]; [email protected]Search for more papers by this authorCorresponding Author
Cheng-He Zhou
Institute of Bioorganic & Medicinal Chemistry, Key Laboratory of Applied Chemistry of Chongqing Municipality, School of Chemistry and, Chemical Engineering, Southwest University, Chongqing, 400715 China
E-mail: [email protected]; [email protected]Search for more papers by this authorQian-Yue Li,
Chun-Mei Zeng,
Yao Chen,
Nisar Ahmad,
Shao-Lin Zhang,
Cheng-He Zhou,
Qian-Yue Li
Institute of Bioorganic & Medicinal Chemistry, Key Laboratory of Applied Chemistry of Chongqing Municipality, School of Chemistry and, Chemical Engineering, Southwest University, Chongqing, 400715 China
These authors contributed equally to this work.
Search for more papers by this authorChun-Mei Zeng
Institute of Bioorganic & Medicinal Chemistry, Key Laboratory of Applied Chemistry of Chongqing Municipality, School of Chemistry and, Chemical Engineering, Southwest University, Chongqing, 400715 China
These authors contributed equally to this work.
Search for more papers by this authorYao Chen
Institute of Bioorganic & Medicinal Chemistry, Key Laboratory of Applied Chemistry of Chongqing Municipality, School of Chemistry and, Chemical Engineering, Southwest University, Chongqing, 400715 China
These authors contributed equally to this work.
Search for more papers by this authorNisar Ahmad
Institute of Bioorganic & Medicinal Chemistry, Key Laboratory of Applied Chemistry of Chongqing Municipality, School of Chemistry and, Chemical Engineering, Southwest University, Chongqing, 400715 China
Search for more papers by this authorCorresponding Author
Shao-Lin Zhang
School of Pharmaceutical Sciences, Chongqing Key Laboratory of Natural Product Synthesis and Drug Research, Chongqing University, Chongqing, 401331 China
E-mail: [email protected]; [email protected]Search for more papers by this authorCorresponding Author
Cheng-He Zhou
Institute of Bioorganic & Medicinal Chemistry, Key Laboratory of Applied Chemistry of Chongqing Municipality, School of Chemistry and, Chemical Engineering, Southwest University, Chongqing, 400715 China
E-mail: [email protected]; [email protected]Search for more papers by this authorFirst published: 20 May 2025
Comprehensive Summary
A unique type of natural coumarin skeleton-based thiazolylbenzonitriles as novel structural scaffolds to exert potential multitargeting supramolecular antibacterial behavior was developed for the first time from resorcinol through multi-step reactions. All the new compounds were characterized by NMR and HRMS spectra. Structure-activity relationships revealed that the ethoxycarbonyl group was the optimal substituent to exert the effective supramolecular antibacterial action of benzopyronyl thiazolylbenzonitriles (BTBs), and BTB 13a gave an extremely low MIC value of 0.002 mM against Staphylococcus aureus 29213, being 3-fold more active than norfloxacin. Compound 13a exerting the most effective supramolecular antibacterial behaviour possessed favourable druggability with no obvious haemolysis, acceptable cytotoxicity and low propensity to induce bacterial resistance. A series of medicinal chemobiological evaluations disclosed that BTB 13a could not only intercalate into DNA to produce stable biosupramolecular complexes to block DNA replication, and form biosupermolecules with DNA gyrase, but also disturb cell membrane to tempt leakage of intracellular contents, fluctuate the metabolism and induce oxidative stress, finally resulting in bacterial cell death. Moreover, the promising BTB 13a exhibited good in vivo antibacterial efficacy against Staphylococcus aureus 29213. These results implied that benzopyronyl thiazolylbenzonitriles possessed large promise as novel structural antibacterial members to combat Staphylococcus aureus 29213.
Supporting Information
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Appendix S1: Supporting Information |
Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.
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