SINTESIS DAN UJI SITOTOKSISITAS 7,8-DIHIDROKSI-4'-METOKSIISOFLAVON TERHADAP SEL KANKER SERVIKS HeLa DAN KOLON WiDr SECARA IN VITRO

FITRIANA INDAH L., Prof. Drs. Sabirin Matsjeh, Ph.D.;Dra. Tutik Dwi Wahyuningsih, M.Si., Ph.D.

2015 | Tesis | S2 Ilmu Kimia

Sintesis 7,8-dihidroksi-4'-metoksiisoflavon dari bahan awal p-anisaldehida telah dilakukan melalui jalur deoksibenzoin. Sintesis diawali dengan mengkonversi p-anisaldehida melalui beberapa tahap reaksi yaitu: reduksi alkohol, brominasi, nitrilisasi dan hidrolisis basa menghasilkan 4-metoksibenzil karboksilat. Senyawa 2,3,4-trihidroksifenil-4'-metoksibenzil keton (deoksibenzoin) diperoleh dari reaksi kondensasi Friedel-Crafts antara 4-metoksibenzil karboksilat, pirogalol dan reagen BF3·Et2O. Produk akhir, 7,8-dihidroksi-4'-metoksiisoflavon dihasilkan dari reaksi antara deoksibenzoin dan reagen BF3·Et2O/DMF/POCl3, sebagai reagen penambah satu atom karbon dan proses siklisasi. Semua produk hasil sintesis dianalisis strukturnya menggunakan spektrometer FTIR, GC-MS, 1H- dan 13C-NMR. Senyawa 7,8-dihidroksi-4'-metoksiisoflavon diuji aktivitas sitotoksiknya sebagai agen antikanker terhadap sel kanker serviks HeLa dan kolon WiDr secara in vitro dengan metode MTT. Hasil penelitian menunjukkan bahwa 4-metoksibenzil karboksilat, 2,3,4-trihidroksifenil-4'-metoksibenzil keton, dan 7,8-dihidroksi-4'-metoksiisoflavon diperoleh dengan rendemen berurutan sebesar 83, 93 dan 88%. Hasil uji sitotoksisitas terhadap 7,8-dihidroksi-4'-metoksiisoflavon mengindikasikan bahwa isoflavon cukup aktif dalam menghambat pertumbuhan sel kanker serviks HeLa dan kolon WiDr dengan nilai IC50 secara berurutan sebesar 37,07 dan 52,36 µg/mL.

Synthesis of 7,8-dihydroxy-4'-methoxyisoflavone from starting material p-anisaldehyde has been done by deoxybenzoin pathways. The synthesis was started by converting p-anisaldehyde via several steps of reaction, i.e alcohol reduction, bromination, nitrilisation and hydrolysis in alkaline condition to give 4-methoxybenzyl carboxylic acid. The compound of 2,3,4-trihydroxyphenyl-4'-methoxybenzyl ketone (deoxybenzoin) was obtained from Friedel-Crafts condensation reaction between 4-methoxybenzyl carboxylic acid, pyrogallol and BF3·Et2O. The final product, 7,8-dihydroxy-4'-methoxyisoflavone, was resulted from reaction between deoxybenzoin and BF3·Et2O/DMF/POCl3 reagents, as the reagents for addition of one carbon atom and cyclization process. The structures of all products were analyzed using FTIR, GC-MS, 1H- and 13C-NMR spectrometers. The cytotoxicity of 7,8-dihydroxy-4'-methoxyisoflavone was tested in vitro against HeLa cervical and WiDr colon cancer cells with MTT method. The results showed that 4-methoxybenzyl carboxylic acid, 2,3,4-trihydroxyphenyl-4'-methoxybenzyl ketone and 7,8-dihydroxy-4'-methoxy isoflavone were yielded in 83, 93 and 88%, respectively. The cytotoxicity test indicated that 7,8-dihydroxy-4'-methoxyisoflavone had a moderate activity for inhibiting the growth of HeLa cervical and WiDr colon cancer cells with IC50 values 37,07 and 52,36 µg/mL, respectively.

Kata Kunci : p-anisaldehida, deoksibenzoin, isoflavon, antikanker