Design, Synthesis and Microbiological Evaluation of Novel Compounds as Potential Staphylococcus aureus Phenylalanine tRNA Synthetase Inhibitors

Elbaramawi, Samar S.; Hughes, Casey; Richards, Jennifer; Gupta, Arya; Ibrahim, Samy M.; Lashine, El-Sayed M.; El-Sadek, Mohamed E.; O’Neill, Alex J.; Wootton, Mandy; Bullard, James M.; Simons, Claire

doi:10.21608/ejchem.2018.4070.1357

Elbaramawi, S., Hughes, C., Richards, J., Gupta, A., Ibrahim, S., Lashine, E., El-Sadek, M., O’Neill, A., Wootton, M., Bullard, J., Simons, C. (2018). Design, Synthesis and Microbiological Evaluation of Novel Compounds as Potential Staphylococcus aureus Phenylalanine tRNA Synthetase Inhibitors. EKB Journal Management System, 61(Conference issue (14th Ibn Sina Arab Conference on Heterocyclic Chemistry and its Applications (ISACHC 2018), 30 March-2 April 2018, Hurgada, Egypt).), 9-25. doi: 10.21608/ejchem.2018.4070.1357

Samar S. Elbaramawi; Casey Hughes; Jennifer Richards; Arya Gupta; Samy M. Ibrahim; El-Sayed M. Lashine; Mohamed E. El-Sadek; Alex J. O’Neill; Mandy Wootton; James M. Bullard; Claire Simons. "Design, Synthesis and Microbiological Evaluation of Novel Compounds as Potential Staphylococcus aureus Phenylalanine tRNA Synthetase Inhibitors". EKB Journal Management System, 61, Conference issue (14th Ibn Sina Arab Conference on Heterocyclic Chemistry and its Applications (ISACHC 2018), 30 March-2 April 2018, Hurgada, Egypt)., 2018, 9-25. doi: 10.21608/ejchem.2018.4070.1357

Elbaramawi, S., Hughes, C., Richards, J., Gupta, A., Ibrahim, S., Lashine, E., El-Sadek, M., O’Neill, A., Wootton, M., Bullard, J., Simons, C. (2018). 'Design, Synthesis and Microbiological Evaluation of Novel Compounds as Potential Staphylococcus aureus Phenylalanine tRNA Synthetase Inhibitors', EKB Journal Management System, 61(Conference issue (14th Ibn Sina Arab Conference on Heterocyclic Chemistry and its Applications (ISACHC 2018), 30 March-2 April 2018, Hurgada, Egypt).), pp. 9-25. doi: 10.21608/ejchem.2018.4070.1357

Elbaramawi, S., Hughes, C., Richards, J., Gupta, A., Ibrahim, S., Lashine, E., El-Sadek, M., O’Neill, A., Wootton, M., Bullard, J., Simons, C. Design, Synthesis and Microbiological Evaluation of Novel Compounds as Potential Staphylococcus aureus Phenylalanine tRNA Synthetase Inhibitors. EKB Journal Management System, 2018; 61(Conference issue (14th Ibn Sina Arab Conference on Heterocyclic Chemistry and its Applications (ISACHC 2018), 30 March-2 April 2018, Hurgada, Egypt).): 9-25. doi: 10.21608/ejchem.2018.4070.1357

	Design, Synthesis and Microbiological Evaluation of Novel Compounds as Potential Staphylococcus aureus Phenylalanine tRNA Synthetase Inhibitors
Egyptian Journal of Chemistry
Article 28, Volume 61, Conference issue (14th Ibn Sina Arab Conference on Heterocyclic Chemistry and its Applications (ISACHC 2018), 30 March-2 April 2018, Hurgada, Egypt)., November and December 2018, Page 9-25 PDF (1.29 MB)
Document Type: Original Article
DOI: 10.21608/ejchem.2018.4070.1357
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Authors
Samar S. Elbaramawi^* ¹^{, 2}; Casey Hughes³; Jennifer Richards⁴; Arya Gupta⁵; Samy M. Ibrahim²; El-Sayed M. Lashine²; Mohamed E. El-Sadek²; Alex J. O’Neill⁵; Mandy Wootton⁴; James M. Bullard³; Claire Simons¹
¹School of Pharmacy and Pharmaceutical Sciences, Cardiff University, King Edward VII Avenue, Cardiff CF10 3NB, UK
²Department of Medicinal Chemistry, Faculty of Pharmacy, Zagazig University, Zagazig P.C. 44519, Egypt
³Department of Chemistry, University of Texas – Rio Grande Valley, 1201 W. University Drive, Edinburg, TX 78541, USA
⁴Specialist Antimicrobial Chemotherapy Unit, University Hospital of Wales, Heath Park, Cardiff CF14 4XW, UK
⁵School of Molecular & Cellular Biology, Garstang Building, Faculty of Biological Sciences, University of Leeds, Leeds LS2 9JT, UK
Abstract
As the resistance of Staphylococcus aureus to antibiotics represents a major threat to global health, anti-infectives with novel mechanisms must be developed. Novel compounds were generated as potential phenylalanine tRNA synthetase (PheRS) inhibitors based on the published homology model of S. aureus PheRS to aid the design process using Molecular Operating Environment (MOE) software. PheRS was selected as it is structurally unique enzyme among the aminoacyl-tRNA syntheases (aaRS), it is considerably different from human cytosolic and human mitochondrial aaRS and it is essential and conserved across bacterial species. The designed compounds were synthesized according to different clear schemes. The compounds were confirmed by 1H NMR, 13C NMR, HRMS and/or microanalysis, and they were microbiologically evaluated.
Keywords
Staphylococcus aureus; Phenylalanine tRNA synthetase; Drug design; Benzimidazole; Indole; Adenine


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