Ahmed Kotb1, Nader S Abutaleb2, Mohamed A Seleem3, Mohamed Hagras1, Haroon Mohammad2, Ashraf Bayoumi1, Adel Ghiaty1, Mohamed N Seleem4, Abdelrahman S Mayhoub5. 1. Department of Pharmaceutical Organic Chemistry, College of Pharmacy, Al-Azhar University, Cairo, 11884, Egypt. 2. Department of Comparative Pathobiology, College of Veterinary Medicine, Purdue University, West Lafayette, 47907, IN, USA. 3. Department of Pharmaceutical Organic Chemistry, College of Pharmacy, Al-Azhar University, Cairo, 11884, Egypt; Department of Pharmaceutical Sciences, University of Nebraska Medical Center, Omaha, NE, 68198, United States. 4. Department of Comparative Pathobiology, College of Veterinary Medicine, Purdue University, West Lafayette, 47907, IN, USA; Purdue Institute of Inflammation, Immunology, and Infectious Disease, West Lafayette, IN, 47907, USA. Electronic address: mseleem@purdue.edu. 5. Department of Pharmaceutical Organic Chemistry, College of Pharmacy, Al-Azhar University, Cairo, 11884, Egypt; University of Science and Technology, Zewail City of Science and Technology, Giza, Egypt. Electronic address: amayhoub@azhar.edu.eg.
Abstract
A new series of phenylthiazoles with t-butyl lipophilic component was synthesized and their antibacterial activity against a panel of multidrug-resistant bacterial pathogens was evaluated. Five compounds demonstrated promising antibacterial activity against methicillin-resistant staphylococcal strains and several vancomycin-resistant staphylococcal and enterococcal species. Additionally, three derivatives 19, 23 and 26 exhibited rapid bactericidal activity, and remarkable ability to disrupt mature biofilm produced by MRSA USA300. More importantly, a resistant mutant to 19 couldn't be isolated after subjecting MRSA to sub-lethal doses for 14 days. Lastly, this new series of phenylthiazoles possesses an advantageous attribute over the first-generation compounds in their stability to hepatic metabolism, with a biological half-life of more than 9 h.
A new series of phenylthiazoles with t-butyl lipophilic component was synthesized and their antibacterial activity against a panel of multidrug-resistant bacterial pathogens was evaluated. Five compounds demonstrated promising antibacterial activity against n class="Chemical">methicillin-resistant staphylococcal strains and several vancomycin-resistant staphylococcal and enterococcal species. Additionally, three derivatives 19, 23 and 26 exhibited rapid bactericidal activity, and remarkable ability to disrupt mature biofilm produced by MRSA USA300. More importantly, a resistant mutant to 19 couldn't be isolated after subjecting MRSA to sub-lethal doses for 14 days. Lastly, this new series of phenylthiazoles possesses an advantageous attribute over the first-generation compounds in their stability to hepatic metabolism, with a biological half-life of more than 9 h.
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