Sintesis Etil 4-(3,5-dimetil-4-fenoksifenil)-6-metil-2-okso-1,2,3,4-tetrahidropirimidin-5-Karboksilat dan Uji Aktivitas Sitotoksik Terhadap Sel T47D
Bilah Samping Artikel
Isi Artikel Utama
Page: 716-725
Abstrak
Kanker menjadi salah satu masalah terbesar kesehatan di dunia termasuk di Indonesia. Penelitian terdahulu telah menemukan jika senyawa DHPM memiliki berbagai aktivitas farmakologi seperti antikanker, antijamur, antibakteri, antituberkulosis, dan antioksidan. Berdasarkan potensi tersebut, menarik untuk dilakukan penelitian lebih lanjut dengan tujuan melakukan sintesis dan mengembangkan turunan senyawa Dihidropirimidinon (DHPM) baru yang berpotensi sebagai antikanker. Sintesis senyawa turunan DHPM dilakukan untuk mendapatkan senyawa etil 4-(4-hidroksi-3,5-dimetilfenil)-6-metil-2-okso-1,2,3,4-tetrahidropirimidine-5-karboksilat (M1). Kemudian senyawa dikembangkan dengan reaksi Mitsunobu menggunakan sonikator untuk mendapatkan senyawa baru etil 4-(3,5-dimetil-4-fenoksifenil)-6-metil-2 okso-1,2,3,4-tetrahidropirimidin-5-karboksilat (C2) yang akan diuji aktivitas sitotoksik terhadap sel kanker T47D. Karakterisasi senyawa dilakukan menggunakan FT-IR, LC-MS, dan melting point. Uji sitotoksik terhadap sel T47D sebagai agen antikanker menggunakan metode MTT [3-(4,5-dimetiltiazol-2-il)-2,5 difeniltetrazolium bromida] assay. Hasil pengujian senyawa C2 memiliki aktivitas sitotoksik dengan IC50 sebesar 202,22 µg/mL. Dari hasil tersebut menunjukkan bahwa senyawa C2 memiliki aktivitas sitotoksik namun sifatnya ringan karena IC50 yang dihasilkan tergolong tinggi. Hasil temuan ini menunjukkan bahwa senyawa C2 memiliki potensi antikanker, tetapi masih diperlukan optimalisasi struktur lebih lanjut untuk meningkatkan efektifitasnya.
Unduhan
Rincian Artikel
Artikel ini berlisensiCreative Commons Attribution-NonCommercial-ShareAlike 4.0 International License.
Referensi
Khaerunnisa AB, Latief S, Syahruddin FI, Royani I, Juhamran RP. Hubungan Tingkat Pengetahuan dan Sikap terhadap Deteksi Dini Kanker Payudara pada Pegawai Rumah Sakit Ibnu Sina Makassar. Fakumi Med J 2023;3:685–94. DOI: https://doi.org/10.33096/fmj.v3i9.291
Bosica G, Cachia F, De Nittis R, Mariotti N. Efficient one-pot synthesis of 3,4-dihydropyrimidin-2(1h)-ones via a three-component biginelli reaction. Molecules 2021;26:1–14. https://doi.org/10.3390/molecules26123753. DOI: https://doi.org/10.3390/molecules26123753
Farooq S, Alharthi FA, Alsalme A, Hussain A, Dar BA, Hamid A, et al. Dihydropyrimidinones: Efficient one-pot green synthesis using Montmorillonite-KSF and evaluation of their cytotoxic activity. R Soc Chem 2020;10:42221–34. https://doi.org/10.1039/d0ra09072g. DOI: https://doi.org/10.1039/D0RA09072G
Khasimbi S, Ali F, Manda K, Sharma A, Chauhan G, Wakode S. Dihydropyrimidinones Scaffold as a Promising Nucleus for Synthetic Profile and Various Therapeutic Targets: A Review. Curr Org Synth 2021;18:270–293. DOI: https://doi.org/10.2174/1570179417666201207215710
Mauricio-Sánchez RA, Salazar R, Luna-Bárcenas JG, Mendoza-Galván A. FTIR Spectroscopy Studies On The Spontaneous Neutralization Of Chitosan Acetate Films By Moisture Conditioning. Vib Spectrosc 2018;94:1–6. https://doi.org/10.1016/j.vibspec.2017.10.005. DOI: https://doi.org/10.1016/j.vibspec.2017.10.005
Fauzi A, Saifudin A, Rullah K. Synthesis of Dihydropyrimidinone (DHPM) Derivatives through a Multicomponent Reaction (MCR) and Their Biological Activity. J Med Chem Sci 2023;6:1810–7. https://doi.org/10.26655/JMCHEMSCI.2023.8.9. DOI: https://doi.org/10.26655/JMCHEMSCI.2023.8.9
Graziano G, Stefanachi A, Contino M, Prieto-Díaz R, Ligresti A, Kumar P, et al. Multicomponent Reaction-Assisted Drug Discovery: A Time- and Cost-Effective Green Approach Speeding Up Identification and Optimization of Anticancer Drugs. vol. 24. 2023. https://doi.org/10.3390/ijms24076581. DOI: https://doi.org/10.3390/ijms24076581
Dzakwan M, Priyanto W. Peningkatan Kelarutan Fisetin Dengan Teknik Kosolvensi. Parapemikir J Ilm Farm 2019;8:5–9. https://doi.org/10.30591/pjif.v8i2.1388. DOI: https://doi.org/10.30591/pjif.v8i2.1388
Hain J, Rollin P, Klaffke W, Lindhorst TK. Anomeric modification of carbohydrates using the Mitsunobu reaction. Beilstein J Org Chem 2018;14:1619–36. https://doi.org/10.3762/bjoc.14.138. DOI: https://doi.org/10.3762/bjoc.14.138
Fletcher S. The Mitsunobu Reaction in the 21st Century. R Soc Chem 2012;00:1–13. https://doi.org/10.1093/jaoac/27.4.588. DOI: https://doi.org/10.1093/jaoac/27.4.588
Lepore SD, He Y. Use of sonication for the coupling of sterically hindered substrates in the phenolic Mitsunobu reaction. J Org Chem 2003;68:8261–3. https://doi.org/10.1021/jo0345751. DOI: https://doi.org/10.1021/jo0345751
Younus HA, Al-Rashida M, Hameed A, Uroos M, Salar U, Rana S, et al. Multicomponent Reactions (MCR) in Medicinal Chemistry: a Patent Review (2010-2020). Expert Opin Ther Pat 2020;31:267–289. DOI: https://doi.org/10.1080/13543776.2021.1858797
Ruswanto R, Wulandari WT, Cantika I, Mardianingrum R. Synthesis and virtual screening of bis-(4-(tert-butyl)-N-(methylcarbamothioyl) benzamide)-Iron (III) complex as an anticancer candidate. Pharmaciana 2021;11:1–14. https://doi.org/10.12928/pharmaciana.v11i1.17837. DOI: https://doi.org/10.12928/pharmaciana.v11i1.17837
Pavia DL, Lampman GM, Kriz GS, Vyvyan JR. Introduction to Spectroscopy, Fourth Edition. USA: 2009. https://doi.org/10.3917/popu.p1977.32n1.0034. DOI: https://doi.org/10.3917/popu.p1977.32n1.0034
Khairan K, Jenie UA, Sudibyo RS. Fragmentation Studies Of Δ6,7-Anhidroeritromisin-A By Liquid Chromatography-Mass Spectroscopy (Lc-Ms). Indones J Chem 2009;9:491–9. https://doi.org/10.22146/ijc.21519. DOI: https://doi.org/10.22146/ijc.21519
Lestari E, Matsjeh S, Swasono RT. Sintesis Senyawa Turunan Khalkon Dan Flavon Berbahan Dasar Vanilin Dan Uji Sitotoksik Terhadap Sel Kanker Serviks (Hela), Sel Kanker Kolon (Widr), Dan Sel Kanker Payudara (T47D) Secara In Vitro. Bimipa 2018;25:53–65.
Nurdiani E, Masriani, Rasmawan R, Muharini R, Sartika RP. Sitotoksisitas dan Selektivitas Fraksi Kayu Batang Simpur Air (Dillenia suffruticosa (Griff.) Martelli) Terhadap Sel Kanker Payudara. Al-Kauniyah J Biol 2024;17:190–200. https://doi.org/10.15408/kauniyah.v17i1.31299. DOI: https://doi.org/10.15408/kauniyah.v17i1.31299
Abdel-Hameed E-SS, Bazaid SA, Shohayeb MM, El-Sayed MM, El-Wakil EA. Phytochemical Studies and Evaluation of Antioxidant, Anticancer and Antimicrobial Properties of Conocarpus erectus L. Growing in Taif, Saudi Arabia. European J Med Plants 2012;2:93–112. https://doi.org/10.9734/ejmp/2012/1040. DOI: https://doi.org/10.9734/EJMP/2012/1040
Lipinski CA, Lombardo F, Dominy BW, Feeney PJ. Experimental and computational approaches to estimate solubility and permeability in drug discovery and development settings. Adv Drug Deliv Rev 2001;46:3–26. https://doi.org/10.1016/j.addr.2012.09.019. DOI: https://doi.org/10.1016/j.addr.2012.09.019