In silico analysis of ciprofloxacin analogs as inhibitors of DNA gyrase of Staphylococcus aureus

• Main Authors: Md. Rakhibul Hasan, Surid Mohammad Chowdhury, Md. Abdul Aziz, Asif Shahriar, Hossain Ahmed, Md. Arif Khan, Shafi Mahmud, Talha Bin Emran
• Format: Article
• Language: English
• Published: Elsevier 2021-01-01
• Series: Informatics in Medicine Unlocked
• Subjects: Antibiotic resistance; Ciprofloxacin; DNA gyrase; Molecular docking; Molecular dynamic simulation
• Online Access: http://www.sciencedirect.com/science/article/pii/S2352914821002240

In this in silico study, thirty-five ciprofloxacin analogs were docked to the active site of DNA gyrase, the prime target of ciprofloxacin type antibiotics. Prior to docking all the structures were optimized using MM2 force field parameters. The study revealed that five candidates, namely 6MePQ_3, 6MePQ_11, A6MePQ_3, HPQ_11, and PQ_7, exhibited promising binding to DNA gyrase. Upon analysis of the ligand-receptor complex, it is also divulged that this binding has been stabilized by the interaction between different neutral, nonpolar, aromatic amino-acid residues of DNA gyrase and the ciprofloxacin analogs. Moreover, the interaction between ciprofloxacin analogs and DNA gyrase was mainly governed by hydrophobic interactions and, to a lesser extent, hydrogen bonds. Halogen bonds, electrostatic interactions, and other types of interactions were almost absent in all cases. Molecular dynamic simulation was performed to recognize the structural variations and the complexes' stability of suggested ligands. This study indicates that 6MePQ_3 forms a stable drug-protein complex. On the other site, Pharmacokinetic filtering done using SwissADME server, reveals that 6MePQ_3 is well absorbed from the GI tract, does not cross BBB and is not a P-gp substrate. But it is possible to check and confirm its all “in silico” pharmacodynamics and pharmacokinetics characteristics in real life by synthesis and subsequent analysis of this ligand.