Journal of Natural Remedies

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Computational Investigation of Plant-based Bioactive Compounds as Inhibitors against Tuberculosis


Affiliations
1 Dr. APJ Kalam Research Lab, Department of Pharmaceutical Chemistry, SRM College of Pharmacy, SRM Institute of Science and Technology, Kattankulathur – 603203, Kancheepuram, Tamil Nadu, India
2 Department of Pharmacognosy and Phytochemistry, Parul Institute of Pharmacy and Research, Parul University, Vadodara – 391760, Gujarat, India
3 Dr. APJ Kalam Research Lab, Department of Pharmaceutical Chemistry, SRM College of Pharmacy, SRM Institute of Science and Technology, Kattankulathur – 603203, Kancheepuram, Tamil Nadu Department of Pharmaceutical Chemistry, SRM College of Pharmacy, SRM Institute of Science and Technology, Kattankulathur – 603203, Kancheepuram, Tamil Nadu, India
 

The objective of the work is to identify a natural origin compound that could have an anti-tubercular effect, thereby preventing the infection in humans using computational approach. Our focus was to find a inhibitor for Enoyl- acyl carrier reductase enzyme and hence chemically diverse scaffolds from plants origin were selected. Admet parameters were performed for the compounds, and the top nine compounds among 50 compounds were found to be non-carcinogenic. The pharmacological predicted activity (Pa) of few compounds such as 14-Deoxy-11,12 didehydroandrographolide, Terflavin B, and Liquirtin was found to be more active when compared with that of the standard reference. Further more the synthesis of these active compounds derivatives can be investigated theoretical followed by its synthesis and evaluation by in vitro activity against the InhA could be of interest.


Keywords

InhA, Liquirtin, Mycobacterium tuberculosis, Molecular Docking, Terflavin B.
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  • Zaman K. Tuberculosis: A global health problem. J Health Popul Nutr. 2010; 28(2):111–3. https://doi.org/10.3329/ jhpn.v28i2.4879. PMid:20411672. PMCid:PMC2980871

  • Chandir S, Hussain H, Salahuddin N, Amir M, Ali F, Lotia I, et al. Extrapulmonary tuberculosis: A retrospective review of 194 cases at a tertiary care hospital in Karachi, Pakistan. J Pak Med Assoc. 2010; 60(2):105–9. PMID: 20209695.

  • Sandhu GK. Tuberculosis: Current situation, challenges and overview of its control programs in India. J Glob Infect Dis. 2011; 3(2):143–50. https://doi.org/10.4103/0974- 777X.81691. PMid:21731301. PMCid:PMC3125027

  • Chadha VK. Progress towards millennium development goals for TB control in seven Asian countries. Indian J Tuberc. 2009; 56(1):30–43.PMID: 19402270.

  • Smith KC, Armitige L, Wanger A. A review of tuberculo- sis: Reflections on the past, present and future of a global epidemic disease. Expert Rev Anti Infect Ther. 2003; 1(3):483–91. https://doi.org/10.1586/14787210.1.3.483. PMid:15482144

  • Singh MM. XDR-TB--danger ahead. Indian J Tuberc. 2007; 54(1):1–2. PMID: 17455416.

  • Gupta R, Thakur B, Singh P, Singh HB, Sharma VD, Katoch VM, et al. Anti-tuberculosis activity of selected medicinal plants against multi-drug resistant Mycobacterium tuber- culosis isolates. Indian J Med Res. 2010; 131:809–13.PMID: 20571171.

  • Houben RM, Dodd PJ. The global burden of latent tuber- culosis infection: A re-estimation using mathematical modelling. PLoS Medicine. 2016; 13(10). https://doi. org/10.1371/journal.pmed.1002152. PMid:27780211. PMCid:PMC5079585

  • Suresh AJ, Nandini S, Sangeetha K, Dhivya LS, Surya PR. Design, synthesis and invitro biological evaluation of pyridine, thiadazole, benzimidazole and acetyl thiophne analogues as anti tubercular agents targeting enzyme InhA. Curr Comput-Aided. 2020. https://doi.org/10.2174/157340 9916666200724152827. PMid:32713342

  • Suresh J, Baek SC, Ramakrishnan SP, Kim H, Mathew B. Discovery of potent and reversible MAO-B inhibi- tors as furanochalcones. Int J Biol Macromol. 2018; 108:660–4. https://doi.org/10.1016/j.ijbiomac.2017.11.159. PMid:29195801

  • Sander T, Freyss J, von Korff M, Reich JR, Rufener C. OSIRIS, an entirely in-house developed drug discovery informatics system. J Chem Inf Model. 2009; 49(2):232–46. https://doi.org/10.1021/ci800305f. PMid:19434825

  • Sabarathinam S, Vijayakumar TM. Assessment of herb- drug interactions based on the pharmacokinetic changes of probe drug, midazolam. Drug Metab Lett. 2021; 14(1):5–8. https://doi.org/10.2174/1872312814666201112122110. PMid:33183217

  • Sabarathinam S, Vijayakumar TM. A short exploration of selected sensitive CYP3A4 substrates (probe drug). Drug Metab Lett. 2021; 14(1):2–4. https://doi.org/10.2174/18723 12814666200811110024. PMid:32781977

  • Mittal M, Goel RK, Bhargava G, Mahajan MP. PASS-assisted exploration of antidepressant activity of 1,3,4-trisubsti- tuted-beta-lactam derivatives. Bioorganic Med Chem Lett. 2008; 18(20):5347–9. https://doi.org/10.1016/j. bmcl.2008.09.064. PMid:18835165

  • Tucker EW, Dooley KE. Preclinical tools for the evalua- tion of tuberculosis treatment regimens for children. Int J Tuberc Lung Dis. 2018; 22(5):7–14. https://doi.org/10.5588/ ijtld.17.0354. PMid:29665948. PMCid: PMC7577428

  • Maiolini M, Gause S, Taylor J, Steakin T, Shipp G, Lamichhane P, et al. The war against tuberculosis: A review of natural compounds and their derivatives. Molecules (Basel, Switzerland). 2020; 25(13). https://doi.org/10.3390/ molecules25133011. PMid:32630150. PMCid:PMC7412169

  • Aanouz I, Belhassan A, El-Khatabi K, Lakhlifi T, El-Ldrissi M, Bouachrine M. Moroccan Medicinal plants as inhibitors against SARS-CoV-2 main protease: Computational investigations. J Biomol Struct Dyn. 2021; 39(8):2971-9. https:// doi.org/10.1080/07391102.2020.1758790. PMid:32306860. PMCid:PMC7212546

  • Gutierrez-Lugo MT, Bewley CA. Natural products, small molecules, and genetics in tuberculosis drug development. J Med Chem. 2008; 51(9):2606–12. https://doi.org/10.1021/ jm070719i. PMid:18393405. PMCid:PMC6260804

  • Borad MA, Jethava DJ, Bhoi MN, Patel CN, Pandya HA, Patel HD. Novel isoniazid-spirooxindole derivatives: design, synthesis, biological evaluation, in silico ADMET predic- tion and computational studies. J Mol Struct. 2020; 1222. https://doi.org/10.1016/j.molstruc.2020.128881

  • Guan L, Yang H, Cai Y, Sun L, Di P, Li W, et al. ADMET- score - a comprehensive scoring function for evaluation of chemical drug-likeness. Medchemcomm. 2018; 10(1):148– 57. https://doi.org/10.1039/C8MD00472B. PMid:30774861. PMCid:PMC6350845


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  • Computational Investigation of Plant-based Bioactive Compounds as Inhibitors against Tuberculosis

Abstract Views: 152  |  PDF Views: 90

Authors

L. S. Dhivya
Dr. APJ Kalam Research Lab, Department of Pharmaceutical Chemistry, SRM College of Pharmacy, SRM Institute of Science and Technology, Kattankulathur – 603203, Kancheepuram, Tamil Nadu, India
M. K. Mohan Maruga Raja
Department of Pharmacognosy and Phytochemistry, Parul Institute of Pharmacy and Research, Parul University, Vadodara – 391760, Gujarat, India
M. K. Kathiravan
Dr. APJ Kalam Research Lab, Department of Pharmaceutical Chemistry, SRM College of Pharmacy, SRM Institute of Science and Technology, Kattankulathur – 603203, Kancheepuram, Tamil Nadu Department of Pharmaceutical Chemistry, SRM College of Pharmacy, SRM Institute of Science and Technology, Kattankulathur – 603203, Kancheepuram, Tamil Nadu, India

Abstract


The objective of the work is to identify a natural origin compound that could have an anti-tubercular effect, thereby preventing the infection in humans using computational approach. Our focus was to find a inhibitor for Enoyl- acyl carrier reductase enzyme and hence chemically diverse scaffolds from plants origin were selected. Admet parameters were performed for the compounds, and the top nine compounds among 50 compounds were found to be non-carcinogenic. The pharmacological predicted activity (Pa) of few compounds such as 14-Deoxy-11,12 didehydroandrographolide, Terflavin B, and Liquirtin was found to be more active when compared with that of the standard reference. Further more the synthesis of these active compounds derivatives can be investigated theoretical followed by its synthesis and evaluation by in vitro activity against the InhA could be of interest.


Keywords


InhA, Liquirtin, Mycobacterium tuberculosis, Molecular Docking, Terflavin B.

References





DOI: https://doi.org/10.18311/jnr%2F2022%2F30194