Molecular docking study of modified isoniazid compounds on mycolic acid synthase in the cell wall of mycobacterium tuberculosis

Jordi  Buannata; Bambang Wijianto; Ihsanul  Arief

doi:10.29303/aca.v7i2.173

Molecular docking study of modified isoniazid compounds on mycolic acid synthase

Studi Molecular Docking Senyawa Isoniazid Termodifikasi pada Sintase Asam Mikolat Dinding Sel Mycobacterium Tuberculosis

Penulis

Jordi Buannata , Bambang Wijianto , Ihsanul Arief

DOI:

10.29303/aca.v7i2.173

Diterbitkan:

2024-10-31

Terbitan:

Vol 7 No 2 (2024)

Kata Kunci:

Molekuler Docking, Anti TBC, Senyawa modifikasi isoniazid, Autodock VINA, ProTox-II

Articles

Unduhan

PDF (English)

Cara Mengutip

Buannata, J. ., Wijianto, B., & Arief, I. . (2024). Studi Molecular Docking Senyawa Isoniazid Termodifikasi pada Sintase Asam Mikolat Dinding Sel Mycobacterium Tuberculosis. Acta Chimica Asiana, 7(2), 471–477. https://doi.org/10.29303/aca.v7i2.173

Unduh Sitasi

Unduhan

Data unduhan belum tersedia.

Metrik

Metrik sedang dimuat ...

Abstrak

Penggunaan isoniazid dalam terapi antituberkulosis dapat menyebabkan mutasi pada gen KatG dan inhA dari Mycobacterium tuberkulosis, yang mengakibatkan berkembangnya resistensi dan memerlukan modifikasi pada senyawa isoniazid. Penelitian ini bertujuan untuk mengkaji potensi dan tingkat toksisitas senyawa hasil modifikasi yaitu asam karboksilat 4-piridin, piridin aldehida, dan metil piridin terhadap reseptor asam mikolat melalui pendekatan molekuler docking. PyRx digunakan untuk proses docking menggunakan protokol dengan kelengkapan 106 dan kotak grid tengah pada X=42.424, Y=22.4321, dan Z=46.6391. Selain itu, situs ProTox-II digunakan untuk menentukan tingkat toksisitas senyawa uji. Hasil yang diperoleh dari penelitian ini terdiri dari nilai afinitas masing-masing senyawa uji: -6, -5,4, dan -5,2 kkal/mol. Tingkat toksisitas senyawa uji adalah sebagai berikut: kelas 5, kelas 4, dan kelas 4. Semua senyawa uji berinteraksi dengan asam amino pada protein target, khususnya dengan angka residu Histidin (HIS A:8), Fenilalanin (PHE A: 142) melalui ikatan hidrogen, Leusin (LEU A:95) melalui ikatan pi-Sigma (π), dan Valin (VAL A:12) melalui ikatan pi-Alkil (π). Kesimpulannya, senyawa asam karboksilat 4-piridin menunjukkan potensi sebagai kandidat obat yang menjanjikan namun memiliki tingkat toksisitas yang tinggi.

Referensi

Venkatappa, T., Shen, D., Ayala, A., Li, R., Sorri, Y., Punnoose, R., Katz, D. (2023).: Association of Mycobacterium tuberculosis infection test results with risk factors for tuberculosis transmission. Journal of Clinical Tuberculosis and Other Mycobacterial Diseases. 33, 100386. https://doi.org/10.1016/j.jctube.2023.100386.

Sampiron, E.G., Calsavara, L.L., Baldin, V.P., Montaholi, D.C., Leme, A.L.D., Namba, D.Y., Alves Olher, V.G., Caleffi-Ferraciolli, K.R., Cardoso, R.F., Siqueira, V.L.D., Vandresen, F., Scodro, R.B. de L. (2023). Isoniazid-N-acylhydrazones as promising compounds for the anti-tuberculosis treatment. Tuberculosis. 141, 102363. https://doi.org/10.1016/j.tube.2023.102363

Chan, C.-Y., Au-Yeang, C., Yew, W.-W., Hui, M., Cheng, A.F.B. (2001). Postantibiotic Effects of Antituberculosis Agents Alone and in Combination. Antimicrob Agents Chemother. 45, 3631–3634. https://doi.org/10.1128/AAC.45.12.3631-3634.2001

Wang Kun, Deng Yimin, Cui Xujie, Chen Mengli, Ou Yanzhe, Li Danting, Guo Minhao, Li Weihui. (2023). PatA Regulates Isoniazid Resistance by Mediating Mycolic Acid Synthesis and Controls Biofilm Formation by Affecting Lipid Synthesis in Mycobacteria. Microbiology Spectrum. 11, e00928-23. https://doi.org/10.1128/spectrum.00928-23

North, E., Jackson, M., Lee, R. (2013). New Approaches to Target the Mycolic Acid Biosynthesis Pathway for the Development of Tuberculosis Therapeutics. CPD. 20, 4357–4378. https://doi.org/10.2174/1381612819666131118203641

Holzheimer, M., Buter, J., Minnaard, A.J. (2021). Chemical Synthesis of Cell Wall Constituents of Mycobacterium tuberculosis. Chem. Rev. 121, 9554–9643. https://doi.org/10.1021/acs.chemrev.1c00043.

PaweŁczyk Jakub, Kremer Laurent. (2014). The Molecular Genetics of Mycolic Acid Biosynthesis. Microbiology Spectrum. 2, 10.1128/microbiolspec.mgm2-0003–2013. https://doi.org/10.1128/microbiolspec.mgm2-0003-2013

Takayama, K., Wang, C., Besra, G.S. (2005). Pathway to Synthesis and Processing of Mycolic Acids in Mycobacterium tuberculosis. Clin Microbiol Rev. 18, 81–101. https://doi.org/10.1128/CMR.18.1.81-101.2005.

Dyas, R.A.A., Wijianto, B., Ih, H. (2023). Docking studies for screening antibacterial compounds of Red Jeringau (Acorus calamus L.) using Shigella flexneri protein as a model system. Acta.Chim.Asiana. 6, 343–350. https://doi.org/10.29303/aca.v6i2.161

Budiarto, D., Wijianto, B., Ih, H. (2023). Study of Anthocyanin Molecule Blocking as Anti-Hypertensive through the Pathway of the Renin-Angiotensin-Aldosterone System (RAAS). Indo. J. Chem. Res. 11, 49–58. https://doi.org/10.30598//ijcr.2023.11-bud

Wijianto, B., Ritmaleni, R., Hari, P., Arief, N. (2020). In silico and in vitro anti-inflammatory evaluation of 2,6-bis-(3’-ethoxy, 4’-hydroxybenzylidene)-cyclohexanone, 2,6-bis-(3’-Bromo,4’-methoxybenzylidene)-cyclohexanone, and 2,6-bis- (3’,4’-dimethoxybenzylidene)-cyclohexanone. J app pharm sci. 10, 99–106. https://doi.org/10.7324/JAPS.2020.10613.

Wijianto, B., . R., Purnomo, H., Nurrochmad, A. (2019). In silico and in vitro assay of HGV analogue as antibacterial. Int J Pharm Pharm Sci. 78–85. https://doi.org/10.22159/ijpps.2019v11i3.30581.

C Malau, N. D., & Azzahra, S. F. (2020). Analysis docking of plasmodium falciparum enoyl acyl carrier protein reductase (pfenr) with organic compunds from virtual screening of herbal database. Acta Chimica Asiana, 3(1), 127-134. Dyas, R. A. A., Wijianto, B., & Hariyanto, I. H. (2023). Docking studies for screening antibacterial compounds of Red Jeringau (Acorus calamus L.) using Shigella flexneri protein as a model system. Acta Chimica Asiana, 6(2), 343-350. https://doi.org/10.4081/jphia.2023.2532

Banerjee, P., Eckert, A.O., Schrey, A.K., Preissner, R. (2018). ProTox-II: a webserver for the prediction of toxicity of chemicals. Nucleic Acids Research. 46, W257–W263. https://doi.org/10.1093/nar/gky318

Cavasotto, C.N., Scardino, V. (2022). Machine Learning Toxicity Prediction: Latest Advances by Toxicity End Point. ACS Omega. 7, 47536–47546. https://doi.org/10.1021/acsomega.2c05693

Yang, S., Kar, S. (2023). Application of artificial intelligence and machine learning in early detection of adverse drug reactions (ADRs) and drug-induced toxicity. Artificial Intelligence Chemistry. 1, 100011. https://doi.org/10.1016/j.aichem.2023.100011

Pires, D.E.V., Blundell, T.L., Ascher, D.B. (2015). pkCSM: Predicting Small-Molecule Pharmacokinetic and Toxicity Properties Using Graph-Based Signatures. J. Med. Chem. 58, 4066–4072. https://doi.org/10.1021/acs.jmedchem.5b00104

Wade, A.D., Huggins, D.J. (2020). Identification of Optimal Ligand Growth Vectors Using an Alchemical Free-Energy Method. J. Chem. Inf. Model. 60, 5580–5594. https://doi.org/10.1021/acs.jcim.0c00610

Du, X., Li, Y., Xia, Y.-L., Ai, S.-M., Liang, J., Sang, P., Ji, X.-L., Liu, S.-Q. (2016). Insights into Protein–Ligand Interactions: Mechanisms, Models, and Methods. IJMS. 17, 144. https://doi.org/10.3390/ijms17020144

Decherchi, S., Cavalli, A. (2020). Thermodynamics and Kinetics of Drug-Target Binding by Molecular Simulation. Chem. Rev. 120, 12788–12833. https://doi.org/10.1021/acs.chemrev.0c00534

Kim, S., Thiessen, P.A., Bolton, E.E., Chen, J., Fu, G., Gindulyte, A., Han, L., He, J., He, S., Shoemaker, B.A., Wang, J., Yu, B., Zhang, J., Bryant, S.H. (2016). PubChem Substance and Compound databases. Nucleic Acids Res. 44, D1202–D1213. https://doi.org/10.1093/nar/gkv951

Kim, S., Chen, J., Cheng, T., Gindulyte, A., He, J., He, S., Li, Q., Shoemaker, B.A., Thiessen, P.A., Yu, B., Zaslavsky, L., Zhang, J., Bolton, E.E. (2023). PubChem 2023 update. Nucleic Acids Research. 51, D1373–D1380. https://doi.org/10.1093/nar/gkac956

Tanbin, S., Ahmad Fuad, F.A., Abdul Hamid, A.A. (2020). Virtual Screening for Potential Inhibitors of Human Hexokinase II for the Development of Anti-Dengue Therapeutics. BioTech. 10, 1. https://doi.org/10.3390/biotech10010001

Lisensi

Artikel ini berlisensiCreative Commons Attribution-NonCommercial-ShareAlike 4.0 International License.

Authors who publish with ACA: Acta Chimica Asiana agree to the following terms:

Authors retain copyright and grant the journal right of first publication with the work simultaneously licensed under a Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International License. This license allows authors to use all articles, data sets, graphics, and appendices in data mining applications, search engines, web sites, blogs, and other platforms by providing an appropriate reference. The journal allows the author(s) to hold the copyright without restrictions and will retain publishing rights without restrictions.
Authors are able to enter into separate, additional contractual arrangements for the non-exclusive distribution of the journal's published version of the work (e.g., post it to an institutional repository or publish it in a book), with an acknowledgement of its initial publication in ACA: Acta Chimica Asiana.
Authors are permitted and encouraged to post their work online (e.g., in institutional repositories or on their website) prior to and during the submission process, as it can lead to productive exchanges, as well as earlier and greater citation of published work (See The Effect of Open Access).

Studi Molecular Docking Senyawa Isoniazid Termodifikasi pada Sintase Asam Mikolat Dinding Sel Mycobacterium Tuberculosis

Penulis

DOI:

Diterbitkan:

Terbitan:

Kata Kunci:

Articles

Unduhan

Cara Mengutip

Unduhan

Metrik

Abstrak

Referensi

Lisensi

Authors who publish with ACA: Acta Chimica Asiana agree to the following terms:

Artikel paling banyak dibaca berdasarkan penulis yang sama

menu

Manuscript Template

Bahasa

Visitor

Terbitan Terkini

Journal Publisher

Contact Us

Information

Share & Follow