Exploring novel aryl/heteroaryl-isosteres of phenylthiazole against multidrug-resistant bacteria.

Autor:	Omara M; Department of Pharmaceutical Organic Chemistry, College of Pharmacy (Girls), Al-Azhar University Cairo Egypt., Hagras M; Department of Pharmaceutical Organic Chemistry, College of Pharmacy (Boys), Al-Azhar University Cairo 11884 Egypt m.hagrs@azhar.edu.eg., Elsebaie MM; Department of Pharmaceutical Organic Chemistry, College of Pharmacy (Boys), Al-Azhar University Cairo 11884 Egypt m.hagrs@azhar.edu.eg., Abutaleb NS; Department of Biomedical Sciences and Pathobiology, Virginia-Maryland College of Veterinary Medicine, Virginia Polytechnic Institute and State University Blacksburg Virginia 24061 USA.; Department of Microbiology and Immunology, Faculty of Pharmacy, Zagazig University Zagazig 44519 Egypt., Nour El-Din HT; Department of Microbiology and Immunology, Faculty of Pharmacy, Cairo University Cairo 11562 Egypt., Mekhail MO; PharmD-Clinical Pharmacy Undergraduate Program, Faculty of Pharmacy, Cairo University Cairo 11562 Egypt., Attia AS; Department of Microbiology and Immunology, Faculty of Pharmacy, Cairo University Cairo 11562 Egypt.; Department of Microbiology and Immunology, School of Pharmacy, Newgiza University Giza Egypt., Seleem MN; Department of Biomedical Sciences and Pathobiology, Virginia-Maryland College of Veterinary Medicine, Virginia Polytechnic Institute and State University Blacksburg Virginia 24061 USA.; Center for One Health Research, Virginia Polytechnic Institute and State University Blacksburg Virginia 24061 USA., Sarg MT; Department of Pharmaceutical Organic Chemistry, College of Pharmacy (Girls), Al-Azhar University Cairo Egypt., Mayhoub AS; Department of Pharmaceutical Organic Chemistry, College of Pharmacy (Boys), Al-Azhar University Cairo 11884 Egypt m.hagrs@azhar.edu.eg.; Nanoscience Program, University of Science and Technology, Zewail City of Science and Technology Giza Egypt.
Jazyk:	angličtina
Zdroj:	RSC advances [RSC Adv] 2023 Jul 06; Vol. 13 (29), pp. 19695-19709. Date of Electronic Publication: 2023 Jul 06 (Print Publication: 2023).
DOI:	10.1039/d3ra02778c
Abstrakt:	Antimicrobial resistance has become a concern as a worldwide threat. A novel scaffold of phenylthiazoles was recently evaluated against multidrug-resistant Staphylococci to control the emergence and spread of antimicrobial resistance, showing good results. Several structural modifications are needed based on the structure-activity relationships (SARs) of this new antibiotic class. Previous studies revealed the existence of two key structural features essential for the antibacterial activity, the guanidine head and lipophilic tail. In this study, a new series of twenty-three phenylthiazole derivatives were synthesized utilizing the Suzuki coupling reaction to explore the lipophilic part. The in vitro antibacterial activity was evaluated against a range of clinical isolates. The three most promising compounds, 7d, 15d and 17d, with potent MIC values against MRSA USA300 were selected for further antimicrobial evaluation. The tested compounds exhibited potent results against the tested MSSA, MRSA, and VRSA strains (concentration: 0.5 to 4 μg mL -1 ). Compound 15d inhibited MRSA USA400 at a concentration of 0.5 μg mL -1 (one-fold more potent than vancomycin) and showed low MIC values against ten clinical isolates, including linezolid-resistant strain MRSA NRS119 and three vancomycin-resistant isolates VRSA 9/10/12. Moreover, compound 15d retained its potent antibacterial activity using the in vivo model by the burden reduction of MRSA USA300 in skin-infected mice. The tested compounds also showed good toxicity profiles and were found to be highly tolerable to Caco-2 cells at concentrations of up to 16 μg mL -1 , with 100% of the cells remaining viable. Competing Interests: All authors declare that they have no conflict of interest. (This journal is © The Royal Society of Chemistry.)
Databáze:	MEDLINE
Externí odkaz:	Zobrazit plný text záznamu