Identification of Novel Inhibitor of Enoyl-Acyl Carrier Protein Reductase (InhA) Enzyme in Mycobacterium tuberculosis from Plant-Derived Metabolites: An In Silico Study

Singh, Kratika; Pandey, Niharika; Ahmad, Firoz; Upadhyay, Tarun Kumar; Islam, Mohammad Hayatul; Alshammari, Nawaf; Saeed, Mohd; Al-Keridis, Lamya Ahmed; Sharma, Rolee

doi:10.3390/antibiotics11081038

Open AccessArticle

Identification of Novel Inhibitor of Enoyl-Acyl Carrier Protein Reductase (InhA) Enzyme in Mycobacterium tuberculosis from Plant-Derived Metabolites: An In Silico Study

by

Kratika Singh

¹

,

Niharika Pandey

¹,

Firoz Ahmad

¹,

Tarun Kumar Upadhyay

²

,

Mohammad Hayatul Islam

³,

Nawaf Alshammari

⁴,

Mohd Saeed

⁴

,

Lamya Ahmed Al-Keridis

^5,* and

Rolee Sharma

^1,6,*

¹

Department of Biosciences, Integral University, IIRC-3, Kursi Road, Lucknow 226026, Uttar Pradesh, India

²

Department of Biotechnology, Parul Institute of Applied Sciences and Animal Cell Culture and Immunobiochemistry Lab, Centre of Research for Development, Parul University, Vadodara 391760, Gujarat, India

³

Department of Biosciences, Integral University, IIRC-5, Kursi Road, Lucknow 226026, Uttar Pradesh, India

⁴

Department of Biology, College of Sciences, University of Ha’il, P.O. Box 2440, Ha’il 81411, Saudi Arabia

⁵

Department of Biology, College of Science, Princess Nourah Bint Abdulrahman University, P.O. Box 84428, Riyadh 11671, Saudi Arabia

⁶

Department of Life Sciences and Biotechnology, C.S.J.M.U (Formerly Kanpur University), Kanpur 208024, Uttar Pradesh, India

^*

Authors to whom correspondence should be addressed.

Antibiotics 2022, 11(8), 1038; https://doi.org/10.3390/antibiotics11081038

Submission received: 25 June 2022 / Revised: 23 July 2022 / Accepted: 26 July 2022 / Published: 1 August 2022

(This article belongs to the Special Issue Design and Preparation of Antimicrobial Agents)

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Abstract

Mycobacterium tuberculosis (M.tb.) enoyl-acyl carrier protein (ACP) reductase (InhA) is validated as a useful target for tuberculosis therapy and is considered an attractive enzyme to drug discovery. This study aimed to identify the novel inhibitor of the InhA enzyme, a potential target of M.tb. involved in the type II fatty acid biosynthesis pathway that controls mycobacterial cell envelope synthesis. We compiled 80 active compounds from Ruta graveolens and citrus plants belonging to the Rutaceae family for pharmacokinetics and molecular docking analyses. The chemical structures of the 80 phytochemicals and the 3D structure of the target protein were retrieved from the PubChem database and RCSB Protein Data Bank, respectively. The evaluation of druglikeness was performed based on Lipinski’s Rule of Five, while the computed phytochemical properties and molecular descriptors were used to predict the ADMET of the compounds. Amongst these, 11 pharmacokinetically-screened compounds were further examined by performing molecular docking analysis with an InhA target using AutoDock 4.2. The docking results showed that gravacridonediol, a major glycosylated natural alkaloid from Ruta graveolens, might possess a promising inhibitory potential against InhA, with a binding energy (B.E.) of −10.80 kcal/mole and inhibition constant (Ki) of 600.24 nM. These contrast those of the known inhibitor triclosan, which has a B.E. of −6.69 kcal/mole and Ki of 12.43 µM. The binding efficiency of gravacridonediol was higher than that of the well-known inhibitor triclosan against the InhA target. The present study shows that the identified natural compound gravacridonediol possesses drug-like properties and also holds promise in inhibiting InhA, a key target enzyme of M.tb.

Keywords: FAS-II; gravacridonediol; InhA; molecular docking; Rutaceae family; tuberculosis

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MDPI and ACS Style

Singh, K.; Pandey, N.; Ahmad, F.; Upadhyay, T.K.; Islam, M.H.; Alshammari, N.; Saeed, M.; Al-Keridis, L.A.; Sharma, R. Identification of Novel Inhibitor of Enoyl-Acyl Carrier Protein Reductase (InhA) Enzyme in Mycobacterium tuberculosis from Plant-Derived Metabolites: An In Silico Study. Antibiotics 2022, 11, 1038. https://doi.org/10.3390/antibiotics11081038

AMA Style

Singh K, Pandey N, Ahmad F, Upadhyay TK, Islam MH, Alshammari N, Saeed M, Al-Keridis LA, Sharma R. Identification of Novel Inhibitor of Enoyl-Acyl Carrier Protein Reductase (InhA) Enzyme in Mycobacterium tuberculosis from Plant-Derived Metabolites: An In Silico Study. Antibiotics. 2022; 11(8):1038. https://doi.org/10.3390/antibiotics11081038

Chicago/Turabian Style

Singh, Kratika, Niharika Pandey, Firoz Ahmad, Tarun Kumar Upadhyay, Mohammad Hayatul Islam, Nawaf Alshammari, Mohd Saeed, Lamya Ahmed Al-Keridis, and Rolee Sharma. 2022. "Identification of Novel Inhibitor of Enoyl-Acyl Carrier Protein Reductase (InhA) Enzyme in Mycobacterium tuberculosis from Plant-Derived Metabolites: An In Silico Study" Antibiotics 11, no. 8: 1038. https://doi.org/10.3390/antibiotics11081038

APA Style

Singh, K., Pandey, N., Ahmad, F., Upadhyay, T. K., Islam, M. H., Alshammari, N., Saeed, M., Al-Keridis, L. A., & Sharma, R. (2022). Identification of Novel Inhibitor of Enoyl-Acyl Carrier Protein Reductase (InhA) Enzyme in Mycobacterium tuberculosis from Plant-Derived Metabolites: An In Silico Study. Antibiotics, 11(8), 1038. https://doi.org/10.3390/antibiotics11081038

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Identification of Novel Inhibitor of Enoyl-Acyl Carrier Protein Reductase (InhA) Enzyme in Mycobacterium tuberculosis from Plant-Derived Metabolites: An In Silico Study

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