Yap, Cheng Hong and Ramle, Abdul Qaiyum and Lim, See Khai and Rames, Avinash and Tay, Sun Tee and Chin, Sek Peng and Kiew, Lik Voon and Tiekink, Edward R. T. and Chee, Chin Fei (2023) Synthesis and Staphylococcus aureus biofilm inhibitory activity of indolenine-substituted pyrazole and pyrimido1,2-b]indazole derivatives. Bioorganic & Medicinal Chemistry, 95. ISSN 0968-0896, DOI https://doi.org/10.1016/j.bmc.2023.117485.
Full text not available from this repository.Abstract
Staphylococcus aureus is a highly adaptable opportunistic pathogen that can form biofilms and generate persister cells, leading to life-threatening infections that are difficult to treat with antibiotics alone. Therefore, there is a need for an effective S. aureus biofilm inhibitor to combat this public health threat. In this study, a small library of indolenine-substituted pyrazoles and pyrimido1,2-b]indazole derivatives were synthesised, of which the hit compound exhibited promising antibiofilm activities against methicillin-susceptible S. aureus (MSSA ATCC 29213) and methicillin-resistant S. aureus (MRSA ATCC 33591) at concentrations significantly lower than the planktonic growth inhibition. The hit compound could prevent biofilm formation and eradicate mature biofilms of MSSA and MRSA, with a minimum biofilm inhibitory concentration (MBIC50) value as low as 1.56 mu g/mL and a minimum biofilm eradication concentration (MBEC50) value as low as 6.25 mu g/mL. The minimum inhibitory concentration (MIC) values of the hit compound against MSSA and MRSA were 50 mu g/mL and 25 mu g/mL, respectively, while the minimum bactericidal concentration (MBC) values against MSSA and MRSA were > 100 mu g/mL. Preliminary structure-activity relationship analysis reveals that the fused benzene ring and COOH group of the hit compound are crucial for the antibiofilm activity. Additionally, the compound was not cytotoxic to human alveolar A549 cells, thus highlighting its potential as a suitable candidate for further development as a S. aureus biofilm inhibitor.
| Item Type: | Article |
|---|---|
| Funders: | Universiti Malaya (ST027-2019) ; (ST029-2020) ; (IIRG003A-19FNW), Sunway University Malaysia (STR-RCTR-RCCM-001-2019) |
| Uncontrolled Keywords: | Antimicrobial agents; Antibiofilm activity; Indazole; Indole; Indolenine; Pyrazole; Pyrimidine; Staphylococcus aureus |
| Subjects: | R Medicine > R Medicine (General) |
| Divisions: | Faculty of Medicine > Department of Pharmacology Faculty of Medicine > Medical Microbiology Department Deputy Vice Chancellor (Research & Innovation) Office > Nanotechnology & Catalysis Research Centre Faculty of Pharmacy > Department of Pharmaceutical Chemistry |
| Depositing User: | Ms. Juhaida Abd Rahim |
| Date Deposited: | 08 Sep 2025 03:17 |
| Last Modified: | 08 Sep 2025 03:17 |
| URI: | http://eprints.um.edu.my/id/eprint/50616 |
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