Mohamed Hagras1, Youssef A Hegazy2, Amr H Elkabbany1, Haroon Mohammad2, Adel Ghiaty1, Tamer M Abdelghany3, 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, Purdue University, College of Veterinary Medicine, West Lafayette, IN, USA. 3. Department of Pharmacology, College of Pharmacy, Al-Azhar University, Cairo 11884, Egypt. 4. Department of Comparative Pathobiology, Purdue University, College of Veterinary Medicine, West Lafayette, IN, USA; Purdue Institute for Inflammation, Immunology, and Infectious Diseases, West Lafayette, IN, USA. 5. Department of Pharmaceutical Organic Chemistry, College of Pharmacy, Al-Azhar University, Cairo 11884, Egypt; Biomedical Sciences, University of Science and Technology, Zewail City of Science and Technology, Giza, Egypt. Electronic address: amayhoub@azhar.edu.eg.
Abstract
A new series of oxadiazolylbiphenylthiazoles was prepared with the objective of improving the limited solubility of first-generation derivatives while maintaining antibacterial activity against drug-resistant Staphylococcus aureus. Studying the structure-activity relationship at the cationic part provided the piperazine-1-carboximidamide derivative 27 with a MIC (MRSA) value of 1.1 μg/mL, bactericidal mode of action, and a 50-fold improvement in aqueous solubility. Additionally, 27 exhibited a wider safety margin against mammalian cells, and most importantly, a significant improvement in oral bioavailability.
A new series of oxadiazolylbiphenylthiazoles was prepared with the objective of improving the limited solubility of first-genen class="Species">ration derivatives while maintaining antibacterial activity against drug-resistant Staphylococcus aureus. Studying the structure-activity relationship at the cationic part provided the piperazine-1-carboximidamide derivative 27 with a MIC (MRSA) value of 1.1 μg/mL, bactericidal mode of action, and a 50-fold improvement in aqueous solubility. Additionally, 27 exhibited a wider safety margin against mammalian cells, and most importantly, a significant improvement in oral bioavailability.
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