Abstract
Tuberculosis (TB) is caused by Mycobacterium tuberculosis (MTB), a highly infectious disease accounting for nearly 1.5 million deaths every year and has been a major global concern. Moreover, resistance to anti-TB drugs is an arduous obstacle to effective prevention, TB care and management. Therefore, incessant attempts are being made to identify novel drug targets and newer anti-tubercular drugs to fight with this deadly pathogen. Increasing resistance, adverse effects and costly treatment by conventional therapeutic agents have been inclining the researchers to search for an alternative source of medicine. In this regard natural compounds have been exploited extensively for their therapeutic interventions targeting cellular machinery of MTB. Glutamate racemase (MurI) is an enzyme involved in peptidoglycan (PG) biosynthesis and has become an attractive target due to its moonlighting property. We screened various classes of natural compounds using computational approach for their binding to MTB-MurI. Shortlisted best docked compounds were evaluated for their functional, structural and anti-mycobacterial activity. The results showed that two flavonoids (naringenin and quercetin) exhibited best binding affinity with MTB-MurI and inhibited the racemization activity with induced structural perturbation. In addition, fluorescence and electron microscopy were employed to confirm the membrane and cell wall damages in mycobacterial cells on exposure to flavonoids. Together, these observations could provide impetus for further research in better understanding of anti-tubercular mechanisms of flavonoids and establishing them as lead molecules for TB treatment.
Highlights
Tuberculosis (TB) is caused by Mycobacterium tuberculosis (MTB), a highly infectious disease accounting for nearly 1.5 million deaths every year and has been a major global concern
The emergent haul of antibiotic resistance, together with declined efforts in the expansion of new antibiotics impelled to the use of natural products as an alternative source for the development of anti-tuberculosis drugs, as they are exceptionally rich in chemical diversity with privileged antimicrobial activity[16]
We analyzed the molecular interactions of protein-ligand which was docked by Discovery studio (DS) 4.0, a commercial software followed by molecular dynamics (MD) simulation studies
Summary
Tuberculosis (TB) is caused by Mycobacterium tuberculosis (MTB), a highly infectious disease accounting for nearly 1.5 million deaths every year and has been a major global concern. Increasing resistance, adverse effects and costly treatment by conventional therapeutic agents have been inclining the researchers to search for an alternative source of medicine In this regard natural compounds have been exploited extensively for their therapeutic interventions targeting cellular machinery of MTB. Fluorescence and electron microscopy were employed to confirm the membrane and cell wall damages in mycobacterial cells on exposure to flavonoids Together, these observations could provide impetus for further research in better understanding of anti-tubercular mechanisms of flavonoids and establishing them as lead molecules for TB treatment. MurI gene encodes for Glutamate racemase enzyme involved in the initial stages of PG biosynthesis and becomes an attractive target for drug designing. The effect of flavonoids on the mycobacterial cell wall has not been well studied
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
