ORIGINAL RESEARCH article
Front. Chem.
Sec. Medicinal and Pharmaceutical Chemistry
Volume 13 - 2025 | doi: 10.3389/fchem.2025.1627186
This article is part of the Research TopicRecent Advances in Synthetic Organic Chemistry at the Biomedical Interface: Honoring Professor Iwao Ojima on the Occasion of his 80th BirthdayView all 20 articles
Design, synthesis, and biological assessment of a novel series of coumarin-tethered thiazole derivatives as potential antibacterial agents
Provisionally accepted
Manal S Ebaid1
Hanaa Farag1
Mohamed Abdelraof1
Abdulrahman M. Saleh2
Mohamed G Thabit3,4
Jaroslaw Dziadek5,6
Ahmed A Youssef7
Ahmed Sabt1*- 1National Research Centre (Egypt), Cairo, Egypt
- 2faculty of pharmacy, cairo university, Cairo, Egypt
- 3Pharmaceutical Chemistry Department, Faculty of Pharmacy, Merit University, Sohag, Egypt, Sohag, Egypt
- 4Pharmaceutical Chemistry Department, Faculty of Pharmacy, Merit University, Sohag, Egypt, cairo, Egypt
- 5Laboratory of Genetics and Physiology of Mycobacterium, Institute of Medical Biology of the Polish Academy of Sciences, Lodz, Poland, Lodz, Poland, Poland
- 6Laboratory of Genetics and Physiology of Mycobacterium, Institute of Medical Biology of the Polish Academy of Sciences, Lodz, Poland, LODZ, Poland
- 7Department of Biochemistry, Faculty of Pharmacy, Egyptian Russian University, Cairo11829, Egypt., cairo, Egypt
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Since the discovery of penicillin in the 1930s, antibiotics have been the primary treatment for bacterial infections. However, antimicrobial resistance (AMR) has escalated due to antibiotics overuse and misuse. To address this concern, a new series of coumarin-thiazole derivatives was synthesized and evaluated against Serratia fonticola, Campylobacter jejuni, Enterococcus faecalis, and Achromobacter xylosoxidans. Most compounds showed selective activity, with compounds 6a and 6c exhibiting potent effects against E. faecalis (MICs: 25, 12.5 μg/mL) and A. xylosoxidans (MICs: 50, 25 μg/mL), comparable to ciprofloxacin. Further studies revealed that 6a and 6c effectively disrupted bacterial biofilms with a low resistance risk. Mechanistically, they induced ROS production, thereby impairing redox homeostasis and reducing lipid peroxidation. Additionally, compound 6a inhibited E. coli DNA gyrase (IC₅₀ = 23.75 μg/mL). Molecular docking studies (PDB ID: 4duh) and dynamics simulations confirmed the stable binding of these compounds to DNA gyrase, suggesting their potential as novel antibacterial agents. These findings highlight promising avenues for the development of new therapeutic agents to combat AMR.
Keywords: Coumarin-thiazole derivatives, Antibacterial activity, Drug Resistance, Biofilm, DNA Gyrase, molecular docking, molecular dynamics
Received: 12 May 2025; Accepted: 21 Aug 2025.
Copyright: © 2025 Ebaid, Farag, Abdelraof, Saleh, Thabit, Dziadek, Youssef and Sabt. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Ahmed Sabt, National Research Centre (Egypt), Cairo, Egypt
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