SINTESIS TURUNAN N-ASETILPIRAZOLINA BERBAHAN DASAR VERATRALDEHIDA DAN 2,4-DIHIDROKSIASETOFENON SERTA UJI SITOTOKSISITASNYA TERHADAP BEBERAPA SEL KANKER

ISTNA CHUNAIFAH, Dra. Tutik Dwi Wahyuningsih, M.Si., Ph.D.

2017 | Skripsi | S1 KIMIA

Sintesis dan uji sitotoksisitas senyawa N-asetilpirazolina dari veratraldehida dan 2,4-dihidroksiasetofenon telah dilakukan. Tahap awal adalah mensintesis kalkon melalui reaksi konsendasi Claisen-Schmidt antara veratraldehida dan 2,4-dihidroksiasetofenon dengan katalis KOH 40% (b/v) menggunakan metode pengadukan dan sonokimia. Tahap selanjutnya, senyawa N-asetilpirazolina disintesis melalui siklokondensasi dengan mereaksikan kalkon dengan hidrazin monohidrat dan asam asetat glasial menggunakan metode refluks dan sonokimia. Elusidasi struktur produk dilakukan menggunakan spektrometer FTIR, direct-MS, KLT-Scanner, 1H- dan 13C-NMR. Uji sitotoksisitas N-asetilpirazolina terhadap sel kanker HeLa, MCF-7, T47D dan WiDr serta sel normal Vero dilakukan menggunakan metode MTT. Produk sintesis kalkon berupa padatan kuning oranye dengan titik lebur 203-205 °C dan rendemen 18,90% menggunakan metode pengadukan serta 27,40% menggunakan sonokimia. Sedangkan produk N-asetilpirazolina dihasilkan padatan putih dengan titik lebur 209-211 °C dan rendemen 89,89% menggunakan metode refluks dan 91,01% menggunakan sonokimia. Uji sitotoksisitas menunjukkan bahwa senyawa N-asetilpirazolina memberikan toksisitas sedang terhadap sel kanker WiDr dan toksisitas lemah terhadap sel kanker HeLa, MCF-7 dan T47D serta tidak bersifat toksik terhadap sel normal Vero. Nilai IC50 N-asetilpirazolina terhadap sel WiDr, HeLa, MCF-7, T47D dan Vero secara berturut-turut 129,80; 481,66; 395,26; 223,23 dan 581,90 µg/mL. Rendahnya aktivitas senyawa N-asetilpirazolina diduga terjadi karena adanya gugus hidroksi pada posisi orto.

Synthesis and cytotoxicity test of N-acetylpyrazoline have been carried out. Chalcone was synthesized from veratraldehyde and 2,4-dihydroxyacetophenone using KOH 40% (w/v) by conventional (stirring) and sonochemistry methods. Synthesis of N-acetylpyrazoline was conducted by cyclocondensation reaction of chalcone, hydrazine hydrate and acetic glacial by conventional (reflux) and sonochemistry methods. The structure elucidation of products was confirmed by FTIR, direct-MS, TLC-Scanner, 1H- and 13C-NMR spectrometers. Cytotoxicity tests of N-acetylpyrazoline against HeLa, MCF-7, T47D and WiDr cancer cells also Vero cell line were conducted by MTT assay. The product of chalcone had m.p. 203-205 °C as yellow solid in 18.40% yield by stirring method and 27.40% yield by sonochemistry method. While N-acetylpyrazoline was yielded as white solid with m.p 209-211 °C in 89.89 and 91.01% by reflux and sonochemistry method, respectively. The research of cytotoxicity test showed that N-acetylpyrazoline has moderate toxicity against WiDr cell, weak toxicity against HeLa, MCF-7 and T47D and no toxicity against Vero cell line. The IC50 values against HeLa, MCF-7, T47D, WiDr and Vero cell were 481.66; 395.26; 223.23; 129.80 and 581.90 µg/mL, respectively. The low toxicities of N-acetylpyrazoline was probably due to the presence of hydroxyl group at ortho position.

Kata Kunci : kalkon, N-asetilpirazolina, sitotoksisitas, veratraldehida