The mechanism of action underlying antibacterial activity of a diterpene quinone derivative against Staphylococcus aureus through the in vitro and in silico assays

Authors

  • Aida Julia Ulfah Graduate Programme in Biomedical Sciences, Faculty of Medicine, Universitas Riau, Pekanbaru, Indonesia
  • Muhammad Yulis Hamidy Department of Pharmacology, Faculty of Medicine, Universitas Riau, Pekanbaru, Indonesia
  • Hilwan Yuda Teruna Department of Chemistry, Faculty of Mathematics and Natural Sciences, Universitas Riau, Pekanbaru, Indonesia https://orcid.org/0000-0001-6363-5239

DOI:

https://doi.org/10.46542/pe.2024.242.8692

Keywords:

Diterpene quinone, In silico assay, In vitro assay, Mechanism of action, Staphylococcus aureus

Abstract

Background: The need for new antibacterials to combat resistance is still constrained by the availability of antibacterials that are safe to use. Diterpene quinone-derived compounds are proven to have antibacterial activity. However,  their mechanism of action is unknown.

Objective: This study aims to determine the mechanism of antibacterial action of a diterpene quinone (6O7AR) on Staphylococcus aureus through in vitro and in silico assays.

Method: MIC tests were performed using microdilution, and MBC determinations were carried out on MHA media. In vitro assays were conducted using membrane permeabilizing with Tris, Triton X-100, and ATPase-inhibiting agents with NaN3. Docking was performed on 2XCT proteins in S. aureus bacteria using AutoDock Vina.

Result: The MIC and MBC results of 6O7AR were 300 μM and 2400 μM, respectively. The in vitro assay result suggested that the antimicrobial activities of 6O7AR were associated with the inhibition of ATPase function and disrupting membrane function. The docking results showed that the compound possessed good interactions with the 2XCT proteins of S. aureus.

Conclusion: 6O7AR exhibited good antibacterial activity. Based on in vitro and in silico assays, the mechanism of action of this compound is related to the disruption of bacterial membrane function, and it has the potential to inhibit the ATPase enzyme and the S. aureus gyrase.

References

Abdissa, N., Frese, M., & Sewald, N. (2017). Antimicrobial abietane-type diterpenoids from Plectranthus punctatus. Molecules, 22(11), 1919. https://doi.org/10.3390/molecules22111919v

Adwan, G., & Mhanna, M. (2009). Synergistic effects of plant extracts and antibiotics on S.aureus strains isolated from clinical speciments. Middle-East Journal of Scientific Research, 3(3), 134‒139. https://idosi.org/mejsr/mejsr3(3)/5.pdf

Darmawijaya, I. P. (2018). The potential of antibacterial in some medicinal plants recorded in the palm oil of taru ppremana. Jurnal Media Sains, 2(1), 43–47. https://jurnal.undhirabali.ac.id/index.php/jms/article/view/356v

GBD 2019 Antimicrobial Resistance Collaborators. (2022). Global mortality associated with 33 bacterial pathogens in 2019: A systematic analysis for the Global Burden of Disease Study 2019. Lancet, 400(10369), 2221–2248.https://doi.org/10.1016/s0140-6736(22)02185-7

Gunawan, S. G. (2012). Pharmacology and theraphy. 5th ed. Badan Penerbit Fakultas Kedokteran Universitas Indonesia.

Klančnik, A., Piskernik, S., Jeršek, B., & Možina, S. S. (2010). Evaluation of diffusion and dilution methods to determine the antibacterial activity of plant extracts. Journal of Microbiological Methods, 81(2), 121–126. https://doi.org/10.1016/j.mimet.2010.02.004

Komatsuzawa, K., Ohta, M., Fujiwara, T., Glanzmann, P., Berger-BächiB, & Suginaka, H. (2000). Tn551-mediated insertional inactivation of the fmtB gene encoding a cell wallassociated protein abolishes methicillin resistance in Staphylococcus aureus. Journal of Antimicrobial Chemotherapy, 45(4), 421–431. https://doi.org/10.1093/jac/45.4.421

Lee, Y-S., Lee, D-Y., Kim, Y. B., Lee, S-W., Cha, S-W., Park, H-W., Kim, G-S., Kwon, D-Y., Lee, M-H., & Han, S-H. (2015). The mechanism underlying the antibacterial activity of shikonin against methicillin-resistant Staphylococcus aureus. Hindawi, 2015, 520578. http://dx.doi.org/10.1155/2015/520578.

Lengauer, T., & Rarey, M. (1996). Computational methods for biomolecular docking. Current Opinion in Structural Biology, 6(3), 402–406. https://doi.org/10.1016/s0959-440x(96)80061-3v

Martins, I. M., Cortés, J. C. G., Munoz, J., Moreno, M. B., Ramos, M., & Ramos, J. A. (2011). Differential activities of three families of specific β(1,3)glucan synthase inhibitors in wild-type and resistant strains of fission yeast. The Journal of Biological Chemistry, 5(286), 3484−3496. https://www.jbc.org/article/S0021-9258(20)54054-4/fulltext

Matias, D., Nicolai, M., Saraiva, L., Pinheiro, R., Faustino, C., Lanza, A. D., Reis, C. P., Stankovic, T., Dinic, J., Pesic, M., & Rijo, P. (2019). Cytotoxic activity of royleanone diterpenes from Plectranthus madagascariensis Benth. Journal American Chemical Society Omega, 4(5), 8094−8103. https://doi.org/10.1021/acsomega.9b00512

Meng, X. Y., Zhang, H. X., Mezei, M., & Cui, M. (2011). Molecular docking: A powerful approach for structure-based drug discovery. Current Computer Aided Drug Design, 7(2), 146–157. https://doi.org/10.2174%2F157340911795677602

Oong, G. C., & Tadi, P. (2023). Chloramphenicol. StatPearls Publishing.

Ortiz, C. L. D., Completo, G. C., Nacario, R. C., & Nellas, R. B. (2019). Potential inhibitors of galactofuranosyltransferase 2 (glft2): Molecular docking, 3D-QSAR, and in silico ADMETox studies. Scientific Reports, 9(1), 1–28. https://doi.org/10.1038/s41598-019-52764-8

Riset Kesehatan Dasar (Riskesdas). (2018). Consumption of medicinal plants. Agency for Health Research and Development. Ministry of Health of the Republic of Indonesia.

Sarker, S. D., Nahar, L., & Kumarasamy, Y. (2007). Microtitre plate-based antibacterial assay incorporating resazurin as an indicator of cell growth and its application in the in vitro antibacterial screening of phytochemicals. Methods, 42(4), 321–324. https://doi.org/10.1016/j.ymeth.2007.01.006v

Soleha, T. U. (2015). Antibiotic sensitivity test. Jurnal Kedokteran Unila, 5(9), 119‒23. https://juke.kedokteran.unila.ac.id/index.php/juke/article/view/644

Teruna, H. Y., Rullah, K., & Khatami, F. (2020). Molecular docking study of the diterpene abieten compound against the main protease enzyme (Mpro) of the coronavirus. Jurnal Farmasi Indonesia, 12(2), 115‒127. https://doi.org/10.35617/jfionline.v12i2.68

WHO. (2017a). Infectious disease.

WHO. (2017b). Prediction of the use of medicinal plants in the world.

Yan, Y., Li, X., Zhang, C., Lv, L., Gao, B., & Li, M. (2021). Research progress on antibacterial activities and mechanisms of natural alkaloids: A Review. Antibiotics, 10(3), 318. https://doi.org/10.3390%2Fantibiotics10030318

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Published

01-04-2024

How to Cite

Ulfah, A. J., Hamidy, M. Y., & Teruna, H. Y. (2024). The mechanism of action underlying antibacterial activity of a diterpene quinone derivative against Staphylococcus aureus through the in vitro and in silico assays. Pharmacy Education, 24(2), p. 86–92. https://doi.org/10.46542/pe.2024.242.8692

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