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 / 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

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.

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.