Modeling the anti-Methicillin-Resistant Staphylococcus aureus (MRSA) Activity of (E)-6-chloro-N²-phenyl-N⁴-(4-Phenyl-5-(Phenyl Diazinyl)-2λ³, 3 λ²- Thiazol-2-yl)-1, 3, 5-Triazine-2,4- Diamine

Abstract

To combat the rise of multidrug-resistant microorganisms like methicillin-resistant Staphylococcus aureus (MRSA), new antibiotic classes are required. Hence, experimental and theoretical calculation utilizing density functional theory (DFT) approach and in-silico molecular docking approach have been exploited in this study on the title molecule: (E)-6-chloro-N²-phenyl-N⁴-(4-phenyl-5-(phenyl diazinyl)-2λ³, 3 λ²- thiazol-2-yl)-1, 3, 5-triazine-2,4- diamine (CPTD) at the B3PW91, ɷB97XD, and PBE0/6-311++G(d, p) level of theory to elucidate its drug like potential against MRSA. Molecular docking analysis was performed on the proposed structure using the following proteins PDB: ID 3T07, 4DKI, 6H50, and 6U3Y and the best binding scores with the ligand were examined to be −9.6 kcal/mol, −7.2 kcal/mol, −6.4 kcal/mol, and −8.6 kcal/mol respectively. However, it’s worth noting that 3T07 and 6U3Y proteins displayed greater binding ability revealing essential amino acids as several active sites were seen adhering efficiently to CPTD. The molecular dynamic simulation corroborated that in the case of protein backbone atoms, it was found that the average RMSD values for complexes of CPTD + 3T07, CPTD + 4DKI, CPTD + 6H5O, and, CPTD + 6U3Y were 2.719 Å, 4.122 Å, 4.021 Å, and 4.619 Å respectively. Thus, it can fervently be stated that the proposed drug substantiates greater antibacterial or inhibitory potential than clindamycin, and hereafter can be developed pharmaceutically to curb MRSA.

Graphical Abstract

Keywords:

• Methicillin resistant Staphylococcus aureus (MRSA)
• DFT
• pharmacokinetic
• molecular docking

Acknowledgements

The authors acknowledge the centre for high performance computing (CHPC), at the University of Johannesburg, South Africa for providing computational resources for this research project.

Disclosure statement

No potential conflict of interest was reported by the author(s).

Author contributions

HL: Project conceptualization, design, and supervision. IB: Writing, results extraction, analysis, and manuscript first draft. GEM, TEG and FOE: Manuscript revision, review, and proofreading, Writing, editing, and analysis. TOUIA, and HP: Writing, editing, and analysis. PN, OS, ECA, EUE, and IJE: Resources, review, and editing.

Additional information

Funding

This research was not funded by any Governmental or Non-governmental agency.