PEMODELAN MOLEKUL DAN MOLEKULAR DINAMIK PUTIK BUNGA SAFRON (Crocus sativus L.) SEBAGAI KANDIDAT OBAT ANTIKANKER PAYUDARA
DOI:
https://doi.org/10.36423/pharmacoscript.v6i2.1391Keywords:
Antikanker payudara, Crocus sativus L., In SilicoAbstract
Kanker payudara adalah tumor ganas yang terbentuk dari sel-sel payudara yang berkembang tanpa terkendali. Doxorubicin merupakan antibiotik golongan antrasiklin yang banyak digunakan untuk kemoterapi pada kanker payudara namun menyebabkan kardiotoksisitas. Tujuan penelitian ini adalah menemukan senyawa sebagai kandidat obat antikanker payudara yang berasal dari metabolit sekunder putik bunga saffron (Crocus sativus L) secara in silico. Analisis metabolit sekunder dilakukan dengan prediksi druglikeness, ADME-Tox, dan uji aktivitas metabolit sekunder dengan metode molecular docking menggunakan program AutoDock Vina dengan reseptor SIRT1 (PDB: 4I5I). Tahap selanjutnya dilakukan uji stabilitas dengan molecular dynamic menggunakan program CHARMM-GUI dan GROMACS yang terdiri dari RMSD, RMSF, jari-jari girasi, SASA dan ikatan hydrogen. Hasil molecular docking menunjukkan metabolit sekunder terbaik putik bunga saffron (Crocus sativus L) yaitu Scutellarein 7-methyl ether 6-glucoside (ΔG = -11,53 kkal/mol) terhadap senyawa pembanding doxorubicin (ΔG = -9,46 kkal/mol). Hasil interaksi ikatan senyawa Scutellarein 7-methyl ether 6-glucoside dengan reseptor 4I5I menunjukkan adanya ikatan hydrogen pada asam amino ASP A:348; ILE A:347; ikatan hidrofobik pada asam amino PHE A:273; PHE A:297. Senyawa Scutellarein 7-methyl ether 6-glucoside selama simulasi menunjukkan hasil RMSD yang relatif stabil dengan selisih nilai RMSD pada kisaran 0,15-0,3 Å; nilai RMSF; nilai jari-jari girasi; nilai SASA, ikatan hidrogen yang relatif stabil tanpa adanya fluktuasi selama waktu simulasi berjalan hingga 20ns. Diharapkan pada penelitian lebih lanjut dilakukan uji in vitro terhadap senyawa Scutellarein 7-methyl ether 6-glucoside yang berpotensi sebagai aktivator SIRT1.References
A. Zeka, J. R, et al. (2015) ‘Inflammatory Markers and Particulate Air Pollution: Characterizing the Pathway to Disease,” International Journal of Epidemiology, Vol. 35, No. 5, 2006, pp. 1347-1354.
Adamson, R. H. (2016) ‘The Acute Lethal Dose 50 (LD 50) of Caffeine in Albino Rats’Regulatory Toxicology and Pharmaceutical, 80, pp. 274-276.
American Cancer Society. Breast Cancer Facts & Figures 2019-2020. Atlanta: American Cancer Society, 2019
Badan Penelitian dan Pengembangan Kesehatan Kementerian Kesehatan Republik Indonesia (2018) Hasil Utama Riskesdas 2018. Jakarta.
Bolhassani A, Khavari A, Bathaie S. Saffron And Natural Carotenoids: Biochemical Activities And Anti-Tumor Effects. Biochimica et Biophysica Acta (BBA). 2014; 1845(1)..
Chikhale, H. and Nerkar, A. (2020) ‘Review on In Silico Techniques an Approach to Drug Discovery’, Current Trends in Pharmacy and Pharmaceutical Chemistry, 2(1), pp. 24-32.
D. Kesuma., Siswandono dan A. Kirtishanti (2022) ‘Molecular Docking And Biological Activity Of N- (4-Methoxy)-Benzoyl-N’-Phenylthiourea And N-(4- Trifluoro)-Benzoyl-N’-Phenylthiourea As Antibreast Cancer Candidates’ , Rasayan J. Chem., 15(2), 1503-1508(2022) http : // doi . org / 10.31788/RJC.2022.1526836
D. Kesuma., Siswandono., Bambang., Marcellino (2020) ‘Synthesis and anticancer evaluation of N-benzoyl-N'-phenyltiourea derivatives against human breast cancer cells (T47D)’ , Journal of Chinese Pharmaceutical Sciences, School of Pharmaceutical Sciences, Peking University. http://www.jcps.ac.cn
Dai X, Hongye C, Zhonghu B, Jia L, Breast Cancer Cell Line Classification and Its Relevance with Breast Tumor Subtyping, Journal of Cancer, 2017, 8(16);3131-41, https : // doi .org /10.7150 /jca .18457.
El-Din, N. A. E. S. S. (2017) ‘Virtual Screening, Drug Likeness, Bioavailability and Docking Studies of Small Molecules of Heterocyclic Sulfonamide’, Word Journal of Pharmacy and Pharmaceutical Sciences, 6(3), pp. 1145-1160.
Elhassan, G. O. and Alfarouk, K.O. (2015) ‘Drug Development: Stages of Drug Development’, J Pharmacovigilance , 3 (3).
Global Cancer Observatory (2022, 24 Oktober). New Global Cancer Data. Diakses pada 20 Desember 2022, dari https://gco.iarc.fr/.
Gumez, A. et al. (2005) ‘Inhibitory Effect of 5-Fluorouracil on Cytochrome P450 2C9 Activity in Cancer Patients’, Clinical Pharmacology & Toxicology, 98, pp.197-200.
Indra Saputra Liambo , Adryan Frisitiohady , Muhammad Hajrul Malaka (2022). Pharmauho: Jurnal Farmasi, Sains, dan Kesehatan “Review: Patofisiologi, Epidemiologi, dan Lini Sel Kanker Payudara”
Jadouali, S.M, et al (2018) ‘Chemical characterization and antioxidant compounds of flower parts of Moroccan crocus sativus L. doi: org/10.1016/j.jssas.2018.03.007
Khorasanchi Z, dkk. Crocus sativus A Natural Food Coloring And Flavoring Has Potent Anti-Tumor Properties. Phytomed. 2018;43:21-27.
Mansoori, et al. (2017) ‘The different mechanisms of cancer drug resistance: A brief review
National Cancer Institute (2016, 21 Desember). Why do Cancer Treatments stop working? Diakses pada 17 November 2022 pada https://www.cancer.gov/about-cancer/treatment/-research/drug-combo-resistance
Pires, D. E. V., Blundell, T. L. and Ascher, D. B. (2015) ‘pkCSM: Predicting Small- Molecule Pharmacokinetic and Toxicity Properties Using Graph-Based Signatures’, Journal of Medical Chemistry, 58, pp. 4066-4072.
Sun, Y.S. Zhao, Z. Zhang-Nv, Y. Fang, X. Hang-Jing, L. Zhi-Yong, Z. Wen, S. Jianmin, J. Ping-Ping, Y. & Han-Ping, Z. (2017). Risk Factors and Preventions of Breast Cancer. International Journal of Biological Sciences,13(11), 1387- 1397, https:// doi.org /10.7150/ijbs.21635.
The Global Cancer Observatory. (2020). WHO Europe. https :// gco .iarc.fr /today/data/factsheets/populations/908- europe-fact-sheets.pdf
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