Title:Exploring the Biochemical Mechanisms of Fluoroquinolone Compounds
against Tuberculosis by Utilizing Molecular Docking and Quantitative
Structure-amino Acid Relationship
Volume: 21
Issue: 9
Author(s): Muneer Alam, Zeeshan Fatima*Sisir Nandi*
Affiliation:
- Department of Pharmaceutical Chemistry, Amity Institute of Pharmacy, Lucknow, Amity University Uttar Pradesh,
Sector 125, Noida, 201313, India
- Department of Pharmaceutical Chemistry, Global Institute of Pharmaceutical Education
and Research, Kashipur, 244713, India
Keywords:
Mycobacterium tuberculosis, fluoroquinolones, molecular docking, structure-based modeling, biochemical mechanisms, quantitative structure-amino acid relationship.
Abstract:
Background: Tuberculosis (TB) is an infectious disease caused by Mycobacterium tuberculosis
(Mtb). It is one of the leading causes of death of 1.5 million people each year. TB can be treated by
directly observed treatment short course (DOTS), but due to multidrug-resistant (MDR) and extensively
drug-resistant (XDR) tuberculosis, consequences can be devastating if the single DOTS dose is missed by
the patient. MDR and XDR-TB require much more attention and time to control the infection. The longer
period of tuberculosis treatment has side effects and it is expensive.
Objectives: This alarming condition demands the development of novel processes to diagnose the disease
in its early stage as well as to produce more promising antimicrobial chemotherapeutics. The current
study aimed to explore molecular mechanisms involving docking simulation-based quantitative structureamino
acid relationship (QSAAR) in order to have a better understanding of the interactions between the
fluoroquinolones and Mtb DNA gyrase.
Methods: In this study, 24 fluoroquinolone (FQ) compounds present in the literature were selected and
docked against the Mtb DNA gyrase. Further, the relationship between the minimum inhibitory concentration
of the compounds and interacting amino acids was assessed using QSAAR.
Results: The study has established a novel method of formulating a quantitative structure-amino acid
relationship. A significant correlation (R-value=0.829) between biological activity and the docked amino
acid residues responsible for producing anti-tubercular activities has been obtained.
Conclusion: The predicted residues captured in the developed model have been explored to report the
Mtb virulence.