SINTESIS KALKON, FLAVON DAN FLAVANON DARI VERATRALDEHIDA SERTA UJI SITOTOKSISITASNYA TERHADAP SEL KANKER HeLa, WiDr, T47D DAN MCF-7 SECARA IN VITRO

AMANATUR RIFQI, Prof. Drs. Sabirin Matsjeh, Ph.D.; Dr. Deni Pranowo, M.Si.

2018 | Tesis | S2 Ilmu Kimia

Senyawa 2',4'-dihidroksi-3,4-dimetoksikalkon (1) telah berhasil disintesis menggunakan metode Claisen-Schmidt dari veratraldehida dan 2',4'-dihidroksi asetofenon dalam pelarut etanol. Reaksi dilakukan selama 48 jam pada temperatur kamar menggunakan katalis basa KOH. Sintesis 7-hidroksi-3',4'-dimetoksiflavon (2) dilakukan melalui reaksi siklisasi oksidatif senyawa 1 menggunakan katalis I2 dalam pelarut DMSO pada kondisi refluks selama 1 jam. Senyawa 7-hidroksi-3',4'-dimetoksiflavanon (3) disintesis melalui isomerisasi senyawa 1 menggunakan katalis natrium asetat maupun asam sulfat pada kondisi refluks selama 12 jam. Karakterisasi senyawa 1, 2 dan 3 menggunakan UV-Vis, GC-MS/MS direct, 1H-NMR dan 13C-NMR. Uji aktivitas senyawa 1, 2 dan 3 terhadap sel kanker HeLa, WiDr, T47D dan MCF-7 dilakukan dengan metode MTT (3-(4,5-dimetiltiazol-2-il)-2,5-difeniltetrazoliumbromida). Hasil penelitian menunjukkan bahwa senyawa 1, 2 dan 3 telah teridentifikasi dan diperoleh rendemen berturut-turut sebesar 49, 23 dan 73%. Hasil uji sitotoksisitas menunjukkan senyawa 1 menghambat sel kanker T47D, WiDr, dan MCF-7 dengan IC50 27,85; 31,60 dan 57,54 mikrogram/mL termasuk dalam kategori sedang. Aktivitas senyawa 2 dan 3 termasuk dalam tidak aktif terhadap sel kanker HeLa, WiDr, T47D maupun MCF-7 (IC50 >100 mikrogram/mL). Hasil uji sitotoksisitas senyawa 1, 2 dan 3 terhadap sel Vero diperoleh IC50 >100 mikrogram/mL. Indeks selektivitas senyawa 1 terhadap WiDr dan T47D sebesar 3,23 dan 3,66.

Compound of 2',4'-dihydroxy-3,4-dimethoxychalcone (1) has been successfully synthesized using the Claisen-Schmidt method of veratraldehyde and 2',4'-dihydroxyacetophenone in ethanol. The reaction was carried out for 48 h under room temperature with KOH as base catalyst. The synthesis of 7-hydroxy-3',4'-dimethoxyflavone (2) by oxidative cyclization reaction of compound 1 using the catalyst I2 in DMSO was carried out under reflux conditions for an hour. The 7-hydroxy-3',4'-dimethoxyflavanone (3) was synthesized by isomerization of compound 1 using a sodium acetate or sulfuric acid as catalyst under reflux conditions for 12 h. The characterization of compounds 1, 2 and 3 was confirmed using UV-Vis, GC-MS/MS direct, 1H-NMR and 13C-NMR. The cytotoxicity of compounds 1, 2 and 3 was tested against HeLa, WiDr, T47D and MCF-7 cancer cells by MTT (3-(4,5-dimethyltiazol-2-yl)-2,5-diphenyltetrazoliumbromida) assay. The results showed that compounds 1, 2 and 3 have been investigated with a successive yield of 49, 23 and 73%. The result of cytotoxicity test showed compound 1 inhibited T47D, WiDr and MCF-7 cancer cells with IC50 27.85, 31.60 and 57.54 mikrogram/mL that into the moderate category. The activities of compounds 2 and 3 belong to inactive category for HeLa, WiDr, T47D and MCF-7 cancer cells (IC50 >100 mikrogram/mL). The result of cytotoxicity test of compounds 1, 2 and 3 against Vero cell obtained IC50 >100 mikrogram/mL. The selectivity index of compound 1 against WiDr and T47D cancer cells were 3.23 and 3.66.

Kata Kunci : chalcone, flavone, flavanone, anticancer, cytotoxicity