Synthesis of Ethyl 4-(3,5-dimethyl-4-phenoxyphenyl)-6-methyl-2-oxo-1,2,3,4-tetrahydropyrimidine-5-carboxylate and Cytotoxic Activity Test Against T47D Cells
Main Article Content
Page: 716-725
Abstract
Cancer is one of the biggest health problems in the world, including in Indonesia. Previous studies have found that DHPM compounds have various pharmacological activities such as anticancer, antifungal, antibacterial, antituberculosis, and antioxidant. Based on this potential, it is interesting to conduct further research with the aim of synthesizing and developing new Dihydropyrimidinone (DHPM) compound derivatives that have potential as anticancer. The synthesis of DHPM derivatives was carried out to obtain ethyl 4-(4-hydroxy-3,5-dimethylphenyl)-6-methyl-2-oxo-1,2,3,4-tetrahydropyrimidine-5-carboxylate (M1). Then the compound was developed by Mitsunobu reaction using a sonicator to obtain a new compound ethyl 4-(3,5-dimethyl-4-phenoxyphenyl)-6-methyl-2-oxo-1,2,3,4-tetrahydropyrimidine-5-carboxylate (C2) which will be tested for cytotoxic activity against T47D cancer cells. Characterization of the compound was done using FT-IR, LC-MS, and melting point. Cytotoxic test against T47D cells as anticancer agent using MTT method [3-(4,5-dimethylthiazol-2-yl)-2,5 diphenyltetrazolium bromide] assay. The test results of compound C2 had cytotoxic activity with IC50 of 202.22 µg/mL. The results showed that compound C2 has cytotoxic activity but it is mild because the IC50 produced is high. These findings suggest that compound C2 has anticancer potential, but further structure optimization is needed to increase its effectiveness.
Downloads
Article Details

This work is licensed under a Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International License.
References
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