Discovery of novel and potent InhA inhibitors by an in silico screening and pharmacokinetic prediction

Chayanin Hanwarinroj, Nareudon Phusi, Bundit Kamsri, Pharit Kamsri, Auradee Punkvang, Sombat Ketrat, Patchreenart Saparpakorn, Supa Hannongbua, Khomson Suttisintong, Prasat Kittakoop, James Spencer, Adrian J Mulholland, Pornpan Pungpo

Research output: Contribution to journalArticle (Academic Journal)peer-review

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Aim: In silico screening approaches were performed to discover novel InhA inhibitors.

Methods: Candidate InhA inhibitors were obtained from the combination of virtual screening and pharmacokinetic prediction. In addition, MM-PBSA, MM-GBSA and WaterSwap methods were performed to investigate binding interactions and binding energy of candidate compounds.

Results: Four candidate compounds with suitable physicochemical, pharmacokinetic, and antibacterial properties are proposed. The crucial interactions of the candidate compounds were H-bond, pi-pi and sigma-pi interactions observed in the InhA binding site. The binding affinity of these compounds was improved by hydrophobic interactions with hydrophobic side chains in InhA pocket.

Conclusion: Four newly identified InhA inhibitors reported in our study could serve as promising hit compounds against M. tuberculosis and may be potentially considered for further experimental studies
Original languageEnglish
Pages (from-to)717-729
Number of pages13
JournalFuture Medicinal Chemistry
Issue number10
Early online date29 Apr 2022
Publication statusPublished - 1 May 2022

Bibliographical note

Funding Information:
This research was supported by the Thailand Research Fund (RSA5980057), RGJ Advanced Programme (RAP60K0009), Ubon Ratchathani University and the Thailand Graduate Institute of Science and Technology (TGIST) (SCA-CO-2560-4375TH and SCA-CO-2563-12135-TH) to C Hanwarinroj and N Phusi, respectively. The financial support from Royal Golden Jubilee PhD Program to B Kamsri (PHD/0132/2559) is gratefully acknowledged. AJ Mulholland and J Spencer also would like to thank the EPSRC for funding via BristolBridge (grant number EP/M027546/1) and CCP-BioSim (grant number EP/M022609/1). The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed. No writing assistance was utilized in the production of this manuscript.

Funding Information:
The authors would like to thank the Center of Excellence for Innovation in Chemistry (PERCH-CIC), Faculty of Science, Ubon Ratchathani University, Faculty of Science, Nakhon Phanom University, Faculty of Science, Kasetsart University, and University of Bristol for their support and facilities. The National Electronics and Computer Technology Center (NECTEC) and the National Nanotechnology Center (NANOTEC) are also gratefully acknowledged for supporting this research.

Publisher Copyright:
© 2022 Newlands Press.


  • Antitubercular Agents/chemistry
  • Bacterial Proteins/chemistry
  • Binding Sites
  • Molecular Docking Simulation
  • Molecular Dynamics Simulation
  • Mycobacterium tuberculosis


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