Exploring biogenic chalcones as DprE1 inhibitors for antitubercular activity via in silico approach
Sanket Rathod1, Pooja Chavan2, Deepak Mahuli3
1Department of Pharmaceutical Chemistry, Bharati Vidyapeeth College of Pharmacy, Kolhapur, 416 013, MS, India. sanket.rathod-copk@bvp.edu.in.
Abstract:
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.
Insights
Drug-resistant tuberculosis (TB) poses a global threat. This study identified a novel biogenic chalcone, ZINC000005158606, with promising in silico anti-TB activity against Mycobacterium tuberculosis targets.
Area of Science:
- Computational chemistry
- Drug discovery
- Tuberculosis research
Background:
- Drug-resistant tuberculosis (TB) is a growing global health crisis, demanding novel therapeutic strategies.
- Mycobacterium tuberculosis causes TB, leading to millions of deaths annually, highlighting the urgent need for new treatments.
- Existing TB control measures are threatened by increasing drug resistance.
Purpose of the Study:
- To identify potential biogenic chalcone compounds effective against drug-resistant TB targets using an in silico approach.
- To evaluate the lead-like properties and binding stability of identified compounds.
- To assess the in silico anti-TB sensitivity of promising candidates.
Main Methods:
- Screening of a biogenic chalcone library against the DprE1 target protein using molecular docking.
- In silico ADMET prediction to assess drug-likeness.
- Pharmacophore modeling to understand key molecular features.
- Molecular dynamics (MD) simulations to evaluate binding stability over 100 ns.
- Comparative in silico anti-TB sensitivity analysis against standard drugs.
Main Results:
- The compound ZINC000005158606 exhibited lead-like properties and significant binding affinity to the DprE1 target.
- Pharmacophore modeling elucidated the essential features of ZINC000005158606 for target interaction.
- MD simulations confirmed the conformational stability of the DprE1-ZINC000005158606 complex.
- ZINC000005158606 demonstrated higher in silico anti-TB sensitivity compared to standard drugs against Mycobacterium tuberculosis.
Conclusions:
- The identified biogenic chalcone, ZINC000005158606, shows significant potential as a lead molecule for developing new anti-TB therapies.
- In silico methods effectively identified a promising compound against drug-resistant Mycobacterium tuberculosis.
- Further experimental validation is warranted to confirm the therapeutic efficacy of ZINC000005158606.
