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

doi:10.4155/fmc-2021-0348

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

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Abstract

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 language	English
Pages (from-to)	717-729
Number of pages	13
Journal	Future Medicinal Chemistry
Volume	14
Issue number	10
Early online date	29 Apr 2022
DOIs	https://doi.org/10.4155/fmc-2021-0348
Publication status	Published - 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.

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

SDG 3 Good Health and Well-being

Research Groups and Themes

Physical & Theoretical

Keywords

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

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Hanwarinroj, C., Phusi, N., Kamsri, B., Kamsri, P., Punkvang, A., Ketrat, S., Saparpakorn, P., Hannongbua, S., Suttisintong, K., Kittakoop, P., Spencer, J., Mulholland, A. J., & Pungpo, P. (2022). Discovery of novel and potent InhA inhibitors by an in silico screening and pharmacokinetic prediction. Future Medicinal Chemistry, 14(10), 717-729. https://doi.org/10.4155/fmc-2021-0348

@article{5dccf57658694aa9a44c156a853cabd9,

title = "Discovery of novel and potent InhA inhibitors by an in silico screening and pharmacokinetic prediction",

abstract = "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",

keywords = "Antitubercular Agents/chemistry, Bacterial Proteins/chemistry, Binding Sites, Molecular Docking Simulation, Molecular Dynamics Simulation, Mycobacterium tuberculosis",

author = "Chayanin Hanwarinroj and Nareudon Phusi and Bundit Kamsri and Pharit Kamsri and Auradee Punkvang and Sombat Ketrat and Patchreenart Saparpakorn and Supa Hannongbua and Khomson Suttisintong and Prasat Kittakoop and James Spencer and Mulholland, \{Adrian J\} and Pornpan Pungpo",

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: {\textcopyright} 2022 Newlands Press.",

year = "2022",

month = may,

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doi = "10.4155/fmc-2021-0348",

language = "English",

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Hanwarinroj, C, Phusi, N, Kamsri, B, Kamsri, P, Punkvang, A, Ketrat, S, Saparpakorn, P, Hannongbua, S, Suttisintong, K, Kittakoop, P, Spencer, J , Mulholland, AJ & Pungpo, P 2022, 'Discovery of novel and potent InhA inhibitors by an in silico screening and pharmacokinetic prediction', Future Medicinal Chemistry, vol. 14, no. 10, pp. 717-729. https://doi.org/10.4155/fmc-2021-0348

TY - JOUR

T1 - Discovery of novel and potent InhA inhibitors by an in silico screening and pharmacokinetic prediction

AU - Hanwarinroj, Chayanin

AU - Phusi, Nareudon

AU - Kamsri, Bundit

AU - Kamsri, Pharit

AU - Punkvang, Auradee

AU - Ketrat, Sombat

AU - Saparpakorn, Patchreenart

AU - Hannongbua, Supa

AU - Suttisintong, Khomson

AU - Kittakoop, Prasat

AU - Spencer, James

AU - Mulholland, Adrian J

AU - Pungpo, Pornpan

N1 - 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.

PY - 2022/5/1

Y1 - 2022/5/1

N2 - 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

AB - 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

KW - Antitubercular Agents/chemistry

KW - Bacterial Proteins/chemistry

KW - Binding Sites

KW - Molecular Docking Simulation

KW - Molecular Dynamics Simulation

KW - Mycobacterium tuberculosis

U2 - 10.4155/fmc-2021-0348

DO - 10.4155/fmc-2021-0348

M3 - Article (Academic Journal)

C2 - 35485258

SN - 1756-8919

VL - 14

SP - 717

EP - 729

JO - Future Medicinal Chemistry

JF - Future Medicinal Chemistry

IS - 10

ER -

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

Abstract

Bibliographical note

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Keywords

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