Drug Design, Development and Therapy (Aug 2022)
Tackling Microbial Resistance with Isatin-Decorated Thiazole Derivatives: Design, Synthesis, and in vitro Evaluation of Antimicrobial and Antibiofilm Activity
Abstract
Refaie M Kassab,1 Sami A Al-Hussain,2 Nooran S Elleboudy,3 Amgad Albohy,4 Magdi EA Zaki,2 Khaled AM Abouzid,5,6 Zeinab A Muhammad7 1Department of Chemistry, Faculty of Science, Cairo University, Giza, 12613, Egypt; 2Department of Chemistry, Faculty of Science, Imam Mohammad Ibn Saud Islamic University (IMSIU), Riyadh, 11623, Saudi Arabia; 3Department of Microbiology and Immunology, The Faculty of Pharmacy, Ain Shams University, Cairo, 11566, Egypt; 4Department of Pharmaceutical Chemistry, Faculty of Pharmacy, The British University in Egypt (BUE), Cairo, 11837, Egypt; 5Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Ain Shams University, Cairo, 11566, Egypt; 6Department of Organic and Medicinal Chemistry, Faculty of Pharmacy, University of Sadat City, Sadat City, Egypt; 7Department of Organic Chemistry, National Organization for Drug Control and Research (NODCAR), Giza, 12311, EgyptCorrespondence: Refaie M Kassab, Department of Chemistry, Faculty of Science, Cairo University, Giza, 12613, Egypt, Tel +20101-336-2594, Fax +20-25685799, Email [email protected] Sami A Al-Hussain, Department of Chemistry, Faculty of Science, Imam Mohammad Ibn Saud Islamic University (IMSIU), Riyadh, 11623, Saudi Arabia, Email [email protected]: Antibiotic resistance is a global threat that has been increasing recently, especially with antibiotic overuse and misuse. The search for new antibiotics is becoming more and more indispensable.Methods: Design and synthesis of isatin derivatives as surrogates of SB-239629, a bacterial tyrosine-tRNA synthetases (TyrRS) inhibitor. The newly synthesized compounds were screened for their antimicrobial and antibiofilm activities. Docking studies were used to investigate potential binding modes of these compounds with TyrRS.Results and Discussion: Newly synthesized isatin-decorated thiazole derivatives (7b, 7d, and 14b) have shown potent antimicrobial activities against E. coli, a representative of gram-negative bacteria. Also, 7f showed the best activity against Methicillin Resistant Staphylococcus aureus (MRSA). In addition, 7h and 11f were found to have antifungal activities against Candida albicans equivalent to that of the reference Nystatin. All the new isatin derivatives with antimicrobial activities were found to exhibit strong biofilm distortion effects at half their minimum inhibitory concentrations (MIC). Moreover, thiazole derivatives 11a-f showed promising biofilm formation inhibition. Finally, molecular docking studies were used to investigate possible binding modes of target compounds with S. aureus and E. coli TyrRS.Conclusion: The novel isatin-decorated thiazole derivatives show strong antimicrobial and antifungal activities with potential action on TyrRS.Keywords: 5-bromoisatin, thiosemicarbazone, hydrazonoyl chlorides, thiazoles, Tyrosyl-tRNA synthetases (TyrRS) inhibitors, antimicrobial, molecular docking, MRSA, antibiofilm
