Potensi Terbentuk Interaksi molekuler pada Fitokimia alami sebagai inhibitor Sap 2 dari Candida albicans: Pendekatan In silico
Abstract
Candida albicans (C. albicans) is a fungus that can live in the digestive tract, mouth, and vagina. C. albicans is the main cause of vulvovaginal candidiasis (VVC), with a percentage of about 80-90%. In addition, C. albicans also causes systemic candidiasis, one of the most common bloodstream infections in hospitalized patients worldwide and is associated with a 40-70% mortality rate. This study aimed to investigate natural phytochemicals potential in inhibiting Sap 2 C. albicans, thereby reducing its virulence factor. The methods used in this study were Sap 2 protein receptor preparation, test ligand preparation, validation and molecular docking of Sap 2, data analysis and visualization, and ADMET prediction using pkCSM. The results of this study are that Silibinin has the closest bond energy to the crystallographic ligands of 8.658 kcal/mol and Apigenin (7.608 kcal/mol), Catechin (7.469 kcal/mol), Resveratrol (6.329 kcal/mol), Gallic acid (5.245 kcal/mol) respectively. Receptors-ligands complex form van der Waals interaction and hydrogen bonds, including hydrogen bond distances. Each test ligand was predicted to bind with the catalytic residues and the S2 S3 and S4 substrate binding pockets from Sap 2. This study concludes that there are molecular interactions of the phytochemicals to inhibit Sap 2.
Downloads
Download data is not yet available.
References
Agistia, D. D., Purnomo, H., Tegar, M., & Nugroho, A. E. (2013). Interaksi Senyawa Aktif Dari Aegle marmelos Correa Sebagai Anti Inflamasi Dengan Reseptor COX-1 Dan COX-2. Traditional Medicine, 18(2), 80–87.
Ali, N. S. M., Salleh, A. B., Leow, T. C., Rahman, R. N. Z. R. A., & Ali, M. S. M. (2020). The Influence of Calcium toward Order/Disorder Conformation of Repeat-in-Toxin (RTX) Structure of Family I.3 Lipase from Pseudomonas fluorescens AMS8. Toxins, 12(579), 1–14. https://doi.org/10.3390/toxins12090579
Borelli, C., Ruge, E., Jung, H. L., Schaller, M., Vogelsang, A., Monod, M., … Maskos, K. (2008). X-ray structures of Sap1 and Sap5: Structural comparison of the secreted aspartic proteinases from Candida albicans. Proteins: Structure, Function and Genetics, 72(4), 1308–1319. https://doi.org/10.1002/prot.22021
Calugi, C., Trabocchi, A., De Bernardis, F., Arancia, S., Navarra, P., Cauda, R., … Guarna, A. (2012). Bicyclic peptidomimetics targeting secreted aspartic protease 2 (SAP2) from Candida albicans reveal a constrained inhibitory chemotype. Bioorganic and Medicinal Chemistry, 20(24), 7206–7213. https://doi.org/10.1016/j.bmc.2012.09.031
Cojocaru, C., & Clima, L. (2020). Polymer assisted ultrafiltration of AO7 anionic dye from aqueous solutions: Experimental design, multivariate optimization, and molecular docking insights. Journal of Membrane Science, 604(February), 118054. https://doi.org/10.1016/j.memsci.2020.118054
Cojocaru, C., Samoila, P., & Pascariu, P. (2019). Chitosan-based magnetic adsorbent for removal of water-soluble anionic dye: Artificial neural network modeling and molecular docking insights. International Journal of Biological Macromolecules, 123, 587–599. https://doi.org/10.1016/j.ijbiomac.2018.11.080
Cutfield, S. M., Dodson, E. J., Anderson, B. F., Moody, P., Marshall, C. J., Sullivan, P. A., & Cutfield, J. F. (1995). The crystal structure of a major secreted aspartic proteinase from Candida albicans in complexes with two inhibitors. Structure, 3(11), 1261–1271. https://doi.org/10.1016/S0969-2126(01)00261-1
Etsè, K. S., Etsè, K. D., Nyssen, P., & Mouithys-Mickalad, A. (2021). Assessment of anti-inflammatory-like, antioxidant activities and molecular docking of three alkynyl-substituted 3-ylidene-dihydrobenzo[d]isothiazole 1,1-dioxide derivatives. Chemico-Biological Interactions, 344(April). https://doi.org/10.1016/j.cbi.2021.109513
Ferrari, I. V. (2021). Open access in silico tools to predict the ADMET profiling and PASS (Prediction of Activity Spectra for Substances of Bioactive compounds of Garlic (Allium sativum L.). BioRxiv. https://doi.org/https://doi.org/10.1101/2021.07.18.452815
Fida, S., Dewi, A. R., & Damayanti, D. S. (2021). Studi In Silico Senyawa Aktif Daun Sirsak (Annona muricata L .) pada Aldose Reductase dan Glutathione Reductase untuk Menghambat Katarak Diabetik. Jurnal Kedokteran Komunitas, 9(2), 1–14.
Frimayanti, N., Djohari, M., & Khusnah, A. N. (2021). Molekular Docking Senyawa Analog Kalkon sebagai Inhibitor untuk Sel Kanker Paru-Paru A549 ( Molecular Docking for Chalcone Analogue Compounds as Inhibitor for Lung Cancer A549 ). Jurnal Ilmu Kefarmasian Indonesia, 19(1), 87–95.
Hardjono, S. (2017). Prediksi Sifat Farmakokinetik, Toksisitas dan Aktivitas Sitotoksik Turunan N-Benzoil-N’-(4-fluorofenil)tiourea sebagai Calon Obat Antikanker melalui Pemodelan Molekul. Jurnal Ilmu Kefarmasian Indonesia, 14(2), 246–255. Retrieved from http://jifi.farmasi.univpancasila.ac.id/index.php/jifi/article/view/38
Hariono, M., & Rollando. (2016). MOLECULAR DOCKING OF COMPOUNDS FROM Chaetomium Sp. AGAINST HUMAN ESTROGEN RECEPTOR ALPHA IN SEARCHING ANTI BREAST CANCER. JURNAL FARMASI SAINS DAN KOMUNITAS, 13(1), 35–43. Retrieved from http://www.tjyybjb.ac.cn/CN/article/downloadArticleFile.do?attachType=PDF&id=9987
Herman, R. (2019). Studi in Silico Lima Senyawa Aktif Sebagai Penghambat Protein Virus Dengue. Jurnal Kefarmasian Indonesia, 9(1), 40–47. https://doi.org/10.22435/jki.v9i1.1157
Kharisma, V. D., Ansori, A. N. M., Widyananda, M. H., Utami, S. L., & Nugraha, A. P. (2020). Molecular simulation: The potency of conserved region on E6 HPV-16 as a binding target of black tea compounds against cervical cancer. Biochemical and Cellular Archives, 20(August), 2795–2802. https://doi.org/10.35124/bca.2020.20.S1.2795
Kumar, Y., Singh, H., & Patel, C. N. (2020). In silico prediction of potential inhibitors for the main protease of SARS-CoV-2 using molecular docking and dynamics simulation based drug-repurposing. Journal of Infection and Public Health, 13(9), 1210–1223. https://doi.org/10.1016/j.jiph.2020.06.016
Li, W., Yu, D., Gao, S., Lin, J., Chen, Z., & Zhao, W. (2014). Role of Candida Albicans-secreted aspartyl proteinases (Saps) in severe early childhood caries. International Journal of Molecular Sciences, 15(6), 10766–10779. https://doi.org/10.3390/ijms150610766
Monroy-Pérez, E., Paniagua-Contreras, G., Vaca-Paniagua, F., Negrete-Abascal, E., & Vaca, S. (2013). SAP Expression in Candida albicans Strains Isolated from Mexican Patients with Vaginal Candidosis. International Journal of Clinical Medicine, 04(01), 25–31. https://doi.org/10.4236/ijcm.2013.41006
Mulatsari, E., Mumpuni, E., & Ramadhan, I. (2019). Skrining Virtual dan Elusidasi Moda Ikatan Senyawa dalam Bawang Putih (Allium Sativum L.) sebagai Penghambat Reseptor Advanced Glycation end Products. Jurnal Ilmu Kefarmasian Indonesia, 17(2), 210–217. https://doi.org/10.35814/jifi.v17i2.749
Nugraheni, D., Agusni, I., & Ervianti, E. (2015). Profil Enzim Secreted Aspartyl Proteinase (SAP) pada Isolat Pasien Kandidiasis Vulvovaginalis (KVV) di RSUD Dr. Soetomo Surabaya. Berkala Ilmu Kesehatan Kulit Dan Kelamin, 27(1), 17–23.
Pires, D. E. V., Blundell, T. L., & Ascher, D. B. (2015). pkCSM: Predicting small-molecule pharmacokinetic and toxicity properties using graph-based signatures. Journal of Medicinal Chemistry, 58(9), 4066–4072. https://doi.org/10.1021/acs.jmedchem.5b00104
Santos, A. L. S., Braga-Silva, L. A., Gonçalves, D. S., Ramos, L. S., Oliveira, S. S. C., Souza, L. O. P., … Branquinha, M. H. (2021). Repositioning lopinavir, an hiv protease inhibitor, as a promising antifungal drug: Lessons learned from candida albicans—in silico, in vitro and in vivo approaches. In Journal of Fungi (Vol. 7). https://doi.org/10.3390/jof7060424
Sari, I. W., Junaidin, J., & Pratiwi, D. (2020). STUDI MOLECULAR DOCKING SENYAWA FLAVONOID HERBA KUMIS KUCING (Orthosiphon stamineus B.) PADA RESEPTOR α-GLUKOSIDASE SEBAGAI ANTIDIABETES TIPE 2. Jurnal Farmagazine, 7(2), 54. https://doi.org/10.47653/farm.v7i2.194
Shakya, A. K. (2019). Natural phytochemicals: Potential anti-HCV targets in silico approach. Journal of Applied Pharmaceutical Science, 9(8), 94–100. https://doi.org/10.7324/JAPS.2019.90813
Shukla, M., & Rohatgi, S. (2020). Vaccination with secreted aspartyl proteinase 2 protein from candida parapsilosis can enhance survival of mice during c. tropicalis-mediated systemic candidiasis. Infection and Immunity, 88(10), 1–21. https://doi.org/10.1128/IAI.00312-20
Srivastava, S., Shree, P., Pandey, H., & Tripathi, Y. B. (2018). Incretin hormones receptor signaling plays the key role in antidiabetic potential of PTY-2 against STZ-induced pancreatitis. Biomedicine and Pharmacotherapy, 97(October 2017), 330–338. https://doi.org/10.1016/j.biopha.2017.10.071
Trivedi, M., Vaidya, D., Patel, C., Prajapati, S., & Bhatt, J. (2020). In silico and in vitro studies to elucidate the role of 1HYN and 1QKI activity in BPA induced toxicity and its amelioration by Gallic acid. Chemosphere. https://doi.org/10.1016/j.chemosphere.2019.125076
Wang, W., Gan, N., Sun, Q., Wu, D., Gan, R., Zhang, M., … Li, H. (2019). Study on the interaction of ertugliflozin with human serum albumin in vitro by multispectroscopic methods, molecular docking, and molecular dynamics simulation. Spectrochimica Acta - Part A: Molecular and Biomolecular Spectroscopy, 219, 83–90. https://doi.org/10.1016/j.saa.2019.04.047
Willems, H. M. E., Bruner, W. S., Barker, K. S., Liu, J., Palmer, G. E., & Peters, B. M. (2017). Overexpression of Candida albicans secreted aspartyl proteinase 2 or 5 is not sufficient for exacerbation of immunopathology in a murine model of vaginitis. Infection and Immunity, 85(10), 1–12. https://doi.org/10.1128/IAI.00248-17
Ali, N. S. M., Salleh, A. B., Leow, T. C., Rahman, R. N. Z. R. A., & Ali, M. S. M. (2020). The Influence of Calcium toward Order/Disorder Conformation of Repeat-in-Toxin (RTX) Structure of Family I.3 Lipase from Pseudomonas fluorescens AMS8. Toxins, 12(579), 1–14. https://doi.org/10.3390/toxins12090579
Borelli, C., Ruge, E., Jung, H. L., Schaller, M., Vogelsang, A., Monod, M., … Maskos, K. (2008). X-ray structures of Sap1 and Sap5: Structural comparison of the secreted aspartic proteinases from Candida albicans. Proteins: Structure, Function and Genetics, 72(4), 1308–1319. https://doi.org/10.1002/prot.22021
Calugi, C., Trabocchi, A., De Bernardis, F., Arancia, S., Navarra, P., Cauda, R., … Guarna, A. (2012). Bicyclic peptidomimetics targeting secreted aspartic protease 2 (SAP2) from Candida albicans reveal a constrained inhibitory chemotype. Bioorganic and Medicinal Chemistry, 20(24), 7206–7213. https://doi.org/10.1016/j.bmc.2012.09.031
Cojocaru, C., & Clima, L. (2020). Polymer assisted ultrafiltration of AO7 anionic dye from aqueous solutions: Experimental design, multivariate optimization, and molecular docking insights. Journal of Membrane Science, 604(February), 118054. https://doi.org/10.1016/j.memsci.2020.118054
Cojocaru, C., Samoila, P., & Pascariu, P. (2019). Chitosan-based magnetic adsorbent for removal of water-soluble anionic dye: Artificial neural network modeling and molecular docking insights. International Journal of Biological Macromolecules, 123, 587–599. https://doi.org/10.1016/j.ijbiomac.2018.11.080
Cutfield, S. M., Dodson, E. J., Anderson, B. F., Moody, P., Marshall, C. J., Sullivan, P. A., & Cutfield, J. F. (1995). The crystal structure of a major secreted aspartic proteinase from Candida albicans in complexes with two inhibitors. Structure, 3(11), 1261–1271. https://doi.org/10.1016/S0969-2126(01)00261-1
Etsè, K. S., Etsè, K. D., Nyssen, P., & Mouithys-Mickalad, A. (2021). Assessment of anti-inflammatory-like, antioxidant activities and molecular docking of three alkynyl-substituted 3-ylidene-dihydrobenzo[d]isothiazole 1,1-dioxide derivatives. Chemico-Biological Interactions, 344(April). https://doi.org/10.1016/j.cbi.2021.109513
Ferrari, I. V. (2021). Open access in silico tools to predict the ADMET profiling and PASS (Prediction of Activity Spectra for Substances of Bioactive compounds of Garlic (Allium sativum L.). BioRxiv. https://doi.org/https://doi.org/10.1101/2021.07.18.452815
Fida, S., Dewi, A. R., & Damayanti, D. S. (2021). Studi In Silico Senyawa Aktif Daun Sirsak (Annona muricata L .) pada Aldose Reductase dan Glutathione Reductase untuk Menghambat Katarak Diabetik. Jurnal Kedokteran Komunitas, 9(2), 1–14.
Frimayanti, N., Djohari, M., & Khusnah, A. N. (2021). Molekular Docking Senyawa Analog Kalkon sebagai Inhibitor untuk Sel Kanker Paru-Paru A549 ( Molecular Docking for Chalcone Analogue Compounds as Inhibitor for Lung Cancer A549 ). Jurnal Ilmu Kefarmasian Indonesia, 19(1), 87–95.
Hardjono, S. (2017). Prediksi Sifat Farmakokinetik, Toksisitas dan Aktivitas Sitotoksik Turunan N-Benzoil-N’-(4-fluorofenil)tiourea sebagai Calon Obat Antikanker melalui Pemodelan Molekul. Jurnal Ilmu Kefarmasian Indonesia, 14(2), 246–255. Retrieved from http://jifi.farmasi.univpancasila.ac.id/index.php/jifi/article/view/38
Hariono, M., & Rollando. (2016). MOLECULAR DOCKING OF COMPOUNDS FROM Chaetomium Sp. AGAINST HUMAN ESTROGEN RECEPTOR ALPHA IN SEARCHING ANTI BREAST CANCER. JURNAL FARMASI SAINS DAN KOMUNITAS, 13(1), 35–43. Retrieved from http://www.tjyybjb.ac.cn/CN/article/downloadArticleFile.do?attachType=PDF&id=9987
Herman, R. (2019). Studi in Silico Lima Senyawa Aktif Sebagai Penghambat Protein Virus Dengue. Jurnal Kefarmasian Indonesia, 9(1), 40–47. https://doi.org/10.22435/jki.v9i1.1157
Kharisma, V. D., Ansori, A. N. M., Widyananda, M. H., Utami, S. L., & Nugraha, A. P. (2020). Molecular simulation: The potency of conserved region on E6 HPV-16 as a binding target of black tea compounds against cervical cancer. Biochemical and Cellular Archives, 20(August), 2795–2802. https://doi.org/10.35124/bca.2020.20.S1.2795
Kumar, Y., Singh, H., & Patel, C. N. (2020). In silico prediction of potential inhibitors for the main protease of SARS-CoV-2 using molecular docking and dynamics simulation based drug-repurposing. Journal of Infection and Public Health, 13(9), 1210–1223. https://doi.org/10.1016/j.jiph.2020.06.016
Li, W., Yu, D., Gao, S., Lin, J., Chen, Z., & Zhao, W. (2014). Role of Candida Albicans-secreted aspartyl proteinases (Saps) in severe early childhood caries. International Journal of Molecular Sciences, 15(6), 10766–10779. https://doi.org/10.3390/ijms150610766
Monroy-Pérez, E., Paniagua-Contreras, G., Vaca-Paniagua, F., Negrete-Abascal, E., & Vaca, S. (2013). SAP Expression in Candida albicans Strains Isolated from Mexican Patients with Vaginal Candidosis. International Journal of Clinical Medicine, 04(01), 25–31. https://doi.org/10.4236/ijcm.2013.41006
Mulatsari, E., Mumpuni, E., & Ramadhan, I. (2019). Skrining Virtual dan Elusidasi Moda Ikatan Senyawa dalam Bawang Putih (Allium Sativum L.) sebagai Penghambat Reseptor Advanced Glycation end Products. Jurnal Ilmu Kefarmasian Indonesia, 17(2), 210–217. https://doi.org/10.35814/jifi.v17i2.749
Nugraheni, D., Agusni, I., & Ervianti, E. (2015). Profil Enzim Secreted Aspartyl Proteinase (SAP) pada Isolat Pasien Kandidiasis Vulvovaginalis (KVV) di RSUD Dr. Soetomo Surabaya. Berkala Ilmu Kesehatan Kulit Dan Kelamin, 27(1), 17–23.
Pires, D. E. V., Blundell, T. L., & Ascher, D. B. (2015). pkCSM: Predicting small-molecule pharmacokinetic and toxicity properties using graph-based signatures. Journal of Medicinal Chemistry, 58(9), 4066–4072. https://doi.org/10.1021/acs.jmedchem.5b00104
Santos, A. L. S., Braga-Silva, L. A., Gonçalves, D. S., Ramos, L. S., Oliveira, S. S. C., Souza, L. O. P., … Branquinha, M. H. (2021). Repositioning lopinavir, an hiv protease inhibitor, as a promising antifungal drug: Lessons learned from candida albicans—in silico, in vitro and in vivo approaches. In Journal of Fungi (Vol. 7). https://doi.org/10.3390/jof7060424
Sari, I. W., Junaidin, J., & Pratiwi, D. (2020). STUDI MOLECULAR DOCKING SENYAWA FLAVONOID HERBA KUMIS KUCING (Orthosiphon stamineus B.) PADA RESEPTOR α-GLUKOSIDASE SEBAGAI ANTIDIABETES TIPE 2. Jurnal Farmagazine, 7(2), 54. https://doi.org/10.47653/farm.v7i2.194
Shakya, A. K. (2019). Natural phytochemicals: Potential anti-HCV targets in silico approach. Journal of Applied Pharmaceutical Science, 9(8), 94–100. https://doi.org/10.7324/JAPS.2019.90813
Shukla, M., & Rohatgi, S. (2020). Vaccination with secreted aspartyl proteinase 2 protein from candida parapsilosis can enhance survival of mice during c. tropicalis-mediated systemic candidiasis. Infection and Immunity, 88(10), 1–21. https://doi.org/10.1128/IAI.00312-20
Srivastava, S., Shree, P., Pandey, H., & Tripathi, Y. B. (2018). Incretin hormones receptor signaling plays the key role in antidiabetic potential of PTY-2 against STZ-induced pancreatitis. Biomedicine and Pharmacotherapy, 97(October 2017), 330–338. https://doi.org/10.1016/j.biopha.2017.10.071
Trivedi, M., Vaidya, D., Patel, C., Prajapati, S., & Bhatt, J. (2020). In silico and in vitro studies to elucidate the role of 1HYN and 1QKI activity in BPA induced toxicity and its amelioration by Gallic acid. Chemosphere. https://doi.org/10.1016/j.chemosphere.2019.125076
Wang, W., Gan, N., Sun, Q., Wu, D., Gan, R., Zhang, M., … Li, H. (2019). Study on the interaction of ertugliflozin with human serum albumin in vitro by multispectroscopic methods, molecular docking, and molecular dynamics simulation. Spectrochimica Acta - Part A: Molecular and Biomolecular Spectroscopy, 219, 83–90. https://doi.org/10.1016/j.saa.2019.04.047
Willems, H. M. E., Bruner, W. S., Barker, K. S., Liu, J., Palmer, G. E., & Peters, B. M. (2017). Overexpression of Candida albicans secreted aspartyl proteinase 2 or 5 is not sufficient for exacerbation of immunopathology in a murine model of vaginitis. Infection and Immunity, 85(10), 1–12. https://doi.org/10.1128/IAI.00248-17
Published
2023-01-31
How to Cite
GHOLAM, Gusnia Meilin; ARTIKA, I Made.
Potensi Terbentuk Interaksi molekuler pada Fitokimia alami sebagai inhibitor Sap 2 dari Candida albicans: Pendekatan In silico.
Jurnal Farmasi Udayana, [S.l.], p. 54-62, jan. 2023.
ISSN 2622-4607.
Available at: <https://ojs.unud.ac.id/index.php/jfu/article/view/84165>. Date accessed: 11 may 2024.
doi: https://doi.org/10.24843/JFU.2022.v11.i02.p04.
Section
Articles
