Exploring biogenic chalcones as DprE1 inhibitors for antitubercular activity via in silico approach

Cases of drug-resistant tuberculosis (TB) have increased worldwide in the last few years, and it is a major threat to global TB control strategies and the human population. Mycobacterium tuberculosis is a common causative agent responsible for increasing cases of TB and as reported by WHO, approximately, 1.5 million death occurred from TB in 2020. Identification of new therapies against drug-resistant TB is an urgent need to be considered primarily. The current investigation aims to find the potential biogenic chalcone against the potential targets of drug-resistant TB via in silico approach. The ligand library of biogenic chalcones was screened against DprE1. Results of molecular docking and in silico ADMET prediction revealed that ZINC000005158606 has lead-like properties against the targeted protein. Pharmacophore modeling was done to identify the pharmacophoric features and their geometric distance present in ZINC000005158606. The binding stability study performed using molecular dynamics (MD) simulation of the DprE1-ZINC000005158606 complex revealed the conformational stability of the complex system over 100 ns with minimum deviation. Further, the in silico anti-TB sensitivity of ZINC000005158606 was found to be higher as compared to the standards against Mycobacterium tuberculosis. The overall in silico investigation indicated the potential of identified hit to act as a lead molecule against Mycobacterium tuberculosis . Graphical Abstract