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

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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.

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All data generated or analyzed during this study are included in this published article and supplementary file.

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Authors and Affiliations

  1. Department of Pharmaceutical Chemistry, Bharati Vidyapeeth College of Pharmacy, Kolhapur, 416 013, MS, India

    Sanket Rathod, Pooja Chavan, Shalini Shinde, Swaranjali Pawar & Prafulla Choudhari

  2. Department of Pharmacology, Bharati Vidyapeeth College of Pharmacy, Kolhapur, 416 013, MS, India

    Deepak Mahuli

  3. Department of Pharmaceutical Chemistry, School of Pharmaceutical Sciences, Sanjay Ghodawat University, Atigre, Kolhapur, 416 013, MS, India

    Sneha Rochlani

  4. Department of Pharmaceutics, Bharati Vidyapeeth College of Pharmacy, Kolhapur, 416 013, MS, India

    Rakesh Dhavale

  5. Department of Management, Institute of Management, Bharati Vidyapeeth Deemed to Be University, Kolhapur, 416 013, MS, India

    Pralhad Mudalkar

  6. Department of Pharmacognosy, Bharati Vidyapeeth College of Pharmacy, Kolhapur, 416 013, MS, India

    Firoj Tamboli

Authors
  1. Sanket Rathod
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  2. Pooja Chavan
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Contributions

Sanket Rathod: conceptualization methodology, software, formal analysis, investigation, resources, data curation, writing (original draft), and visualization. Pooja Chavan: software and writing (original draft). Deepak Mahuli: writing (review and editing); Sneha Rochlani: formal analysis and writing (review and editing). Shalini Shinde: formal analysis and data curation. Swaranjali Pawar: formal analysis and data curation. Prafulla Choudhari: conceptualization, methodology, writing (review and editing), and supervision; Rakesh Dhavale: conceptualization, validation, writing (review and editing), and supervision. Pralhad Mudalkar: writing (review and editing). Firoj Tamboli: writing (review and editing).

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Correspondence to Sanket Rathod or Prafulla Choudhari.

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Rathod, S., Chavan, P., Mahuli, D. et al. Exploring biogenic chalcones as DprE1 inhibitors for antitubercular activity via in silico approach. J Mol Model 29, 113 (2023). https://doi.org/10.1007/s00894-023-05521-8

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