SCREENING OF ASHITABA (ANGELICA KEISKEI K.) COMPOUNDS AS POTENTIAL MYCOBACTERIUM TUBERCULOSIS KASA INHIBITORS

AIYI ASNAWI; ELLIN FEBRINA; WIDHYA ALIGITA; DEWI KURNIA; LA ODE AMAN; ANNE YULIANTINI

doi:10.22159/ijap.2022.v14s5.13

Authors

AIYI ASNAWI Department of Pharmacochemistry, Faculty of Pharmacy, Universitas Bhakti Kencana, Jl. Soekarno-Hatta No. 754, Bandung, 40617, Indonesia
ELLIN FEBRINA Department of Pharmacology and Clinical Pharmacy, Faculty of Pharmacy, Universitas Padjadjaran, Jl. Raya Bandung-Sumedang Km. 21, Jatinangor, 45363, Indonesia
WIDHYA ALIGITA Department of Pharmacochemistry, Faculty of Pharmacy, Universitas Bhakti Kencana, Jl. Soekarno-Hatta No. 754, Bandung, 40617, Indonesia
DEWI KURNIA Department of Pharmacochemistry, Faculty of Pharmacy, Universitas Bhakti Kencana, Jl. Soekarno-Hatta No. 754, Bandung, 40617, Indonesia
LA ODE AMAN Department of Chemistry, Faculty of Mathematics and Natural Science, Universitas Negeri Gorontalo Jl. Jend. Sudirman No. 6 Kota Gorontalo, Gorontalo, 96128, Indonesia
ANNE YULIANTINI Department of Pharmacochemistry, Faculty of Pharmacy, Universitas Bhakti Kencana, Jl. Soekarno-Hatta No. 754, Bandung, 40617, Indonesia

DOI:

https://doi.org/10.22159/ijap.2022.v14s5.13

Keywords:

Ashitaba, In silico, KasA, Mycobacterium tuberculosis, Molecular docking, Molecular dynamics

Abstract

Objective: Tuberculosis (TB) is a major global issue, mainly owing to the emergence of antibiotic-resistant strains of the disease's causative agent, Mycobacterium tuberculosis. The current standard of treatment for tuberculosis entails a prolonged course of antibiotics with toxic side effects and is accompanied by low patient compliance. Therefore, developing and discovering TB medications is critical to obtaining TB drugs that are more effective and sensitive to Mycobacterium tuberculosis. Ashitaba (Angelica keiskei K.) has reported that Ashitaba extract and chalcone have anti-TB properties, but the responsible compound has not been reported yet. This study aimed to identify the profile metabolites present in Ashitaba and their interaction with Mycobacterium tuberculosis KasA.

Methods: To suggest these, we used molecular docking and molecular dynamic to predict the interactions of 40 selected compounds from the Ashitaba against Mycobacterium tuberculosis KasA (PDB ID 2WGE).

Results: The results of molecular docking identified the top two compounds as xanthoangelol I (XAI) and (2E)-1-[4-hydroxy-2-(2-hydroxy-2-propanyl)-2,3-dihydro-1-benzofuran-7-yl]-3-(4-hydroxyphenyl)-2-propen-1-one (4HH), with bond free energies of-12.03 and-11.87 kcal/mol, respectively. Based on the results of molecular dynamics simulations, the XAI was stronger than 4HH in stabilizing complexes with 2WGE with total energy (ΔGbind, MMGBSA) of-54.8512 and-37.8836 kcal/mol, respectively.

Conclusion: It can be concluded that xanthoangelol I (XAI) have the most potent inhibitor of Mycobacterium tuberculosis KasA.

Downloads

Download data is not yet available.

References

Floyd K, Glaziou P, Zumla A, Raviglione M. The global tuberculosis epidemic and progress in care, prevention, and research: an overview in year 3 of the End TB era. Lancet Respir Med. 2018 Apr 1;6(4):299-314. doi: 10.1016/S2213-2600(18)30057-2, PMID 29595511.

Baptista R, Bhowmick S, Nash RJ, Baillie L, Mur LAJ. Target discovery-focused approaches to overcome bottlenecks in the exploitation of antimycobacterial natural products. Future Med Chem. 2018 Apr 1;10(7):811-22. doi: 10.4155/fmc-2017-0273, PMID 29569936.

Slayden RA, Barry CE. The role of KasA and KasB in the biosynthesis of meromycolic acids and isoniazid resistance in Mycobacterium tuberculosis. Tuberculosis (Edinb). 2002;82(4-5):149-60. doi: 10.1054/tube.2002.0333, PMID 12464486.

Slayden RA, Lee RE, Armour JW, Cooper AM, Orme IM, Brennan PJ. Antimycobacterial action of thiolactomycin: an inhibitor of fatty acid and mycolic acid synthesis. Antimicrob Agents Chemother. 1996;40(12):2813-9. doi: 10.1128/AAC.40.12.2813, PMID 9124847.

Kusuma SAF, Iskandar Y, Dewanti MA. The ethanolic extract of ashitaba stem (Angelica keskei [Miq.] Koidz) as future antituberculosis. J Adv Pharm Technol Res. 2018;9(1):37-41. doi: 10.4103/japtr.JAPTR_283_17, PMID 29441323.

Lin YM, Zhou Y, Flavin MT, Zhou LM, Nie W, Chen FC. Chalcones and flavonoids as anti-tuberculosis agents. Bioorg Med Chem. 2002;10(8):2795-802. doi: 10.1016/s0968-0896(02)00094-9, PMID 12057669.

McConkey BJ, Sobolev V, Edelman M. The performance of current methods in ligand–protein docking. Curr Sci. 2002:845-56.

Nursamsiar AA, Kartasasmita RE, Ibrahim S, Tjahjono DH. Synthesis, biological evaluation, and docking analysis of methyl hydroquinone and bromo methyl hydroquinone as potent cyclooxygenase (COX-1 and COX-2) inhibitors. J App Pharm Sci. 2018 Jul 30;8(7):16-20. doi: 10.7324/JAPS.2018.8703/abstract.php?id=2669andsts=2.

A Asnawi, Aman LO, Nursamsiar, A Yuliantini, E Febrina. Molecular docking and molecular dynamic studies: screening phytochemicals of Acalypha Indica Against Braf kinase receptors for potential use in melanocytic tumours. Rasayan J Chem. 2022 Apr;15(2):1352-61. doi: 10.31788/RJC.2022.1526769.

Nursamsiar, Nur S, Febrina E, Asnawi A, Syafiie S. Synthesis and inhibitory activity of curculigoside A derivatives as potential anti-diabetic agents with β-cell apoptosis. J Mol Struct. 2022;1265:133292. doi: 10.1016/j.molstruc.2022.133292.

Li Q, Cheng T, Wang Y, Bryant SH. PubChem as a public resource for drug discovery. Drug Discov Today. 2010 Dec;15(23-24):1052-7. doi: 10.1016/j.drudis.2010.10.003, PMID 20970519.

Luckner SR, Machutta CA, Tonge PJ, Kisker C. Crystal structures of Mycobacterium tuberculosis KasA show mode of action within cell wall biosynthesis and its inhibition by thiolactomycin. Structure. 2009 Jul 7;17(7):1004-13. doi: 10.1016/j.str.2009.04.012, PMID 19604480.

Bitencourt Ferreira G, Pintro VO, de Azevedo WF. Docking with AutoDock4. Methods Mol Biol. 2019;2053:125-48. doi: 10.1007/978-1-4939-9752-7_9, PMID 31452103.

Febrina E, Alamhari RK, Abdulah R, Lestari K, Levita J, Supratman U. Molecular docking and molecular dynamics studies of acalypha Indica L. phytochemical constituents with caspase-3. Int J App Pharm. 2021 Dec 11;13Special Issue 4:210-5. doi: 10.22159/ijap.2021.v13s4.43861.

Kumar P, Capodagli GC, Awasthi D, Shrestha R, Maharaja K, Sukheja P. Synergistic lethality of a binary inhibitor of mycobacterium tuberculosis kasA. mBio. 2018 Nov 1;9(6). doi: 10.1128/mBio.02101-17, PMID 30563908.

Batt SM, Burke CE, Moorey AR, Besra GS. Antibiotics and resistance: the two-sided coin of the mycobacterial cell wall. Cell Surf. 2020 Dec 1;6:100044. doi: 10.1016/j.tcsw.2020.100044, PMID 32995684.