Laporkan Masalah

SINTESIS TURUNAN N-FENIL PIRAZOLINA DARI VERATRALDEHIDA DAN UJI SITOTOKSISITASNYA TERHADAP BEBERAPA SEL KANKER

SETIAWATI, Dr. Tutik Dwi Wahyuningsih, M.Si.; Dr. Deni Pranowo, M.Si.

2018 | Tesis | S2 Ilmu Kimia

Sintesis turunan N-fenil pirazolina dari veratraldehida dan tiga turunan asetofenon serta uji sitotoksisitasnya terhadap sel kanker HeLa, MCF-7, T47D, WiDr telah dilakukan. Sintesis N-fenil pirazolina dilakukan melalui dua tahap yaitu kondensasi aldol silang (Claisen-Schmidt) dan siklokondensasi, serta uji sitotoksisitas senyawa pirazolina terhadap beberapa sel kanker dan sel normal (Vero) dilakukan menggunakan metode 3-(4,5-dimetiltiazol-2-il)-2,5-difenil tetrazolium bromida (MTT). Kondensasi aldol dilakukan dengan cara mereaksikan campuran antara veratraldehida dengan asetofenon, 2-hidroksiasetofenon, 4-hidroksiasetofenon dalam etanol dan katalis NaOH 40% menggunakan metode sonokimia untuk menghasilkan 1-fenil-3-(3',4'-dimetoksifenil)-2-propen-1-on (kalkon A), 1-(2'-hidroksifenil)-3-(3',4'-dimetoksifenil)-2-propen-1-on (kalkon B) dan 1-(4'-hidroksifenil)-3-(3',4'-dimetoksifenil)-2-propen-1-on (kalkon C). Siklisasi kalkon dengan fenilhidrazin dilakukan dengan metode konvensional dan sonokimia untuk menghasilkan 1-fenil-3-(fenil)-5-(3',4'-dimetoksifenil)-2-pirazolina (pirazolina A), 1-fenil-3-(2'-hidroksifenil)-5-(3',4'-dimetoksifenil)-2-pirazolina (pirazolina B), 1-fenil-3-(4'-hidroksifenil)-5-(3',4'-dimetoksifenil)-2-pirazolina (pirazolina C). Semua produk dielusidasi menggunakan FT-IR, GC-MS, 1H- dan 13C-NMR. Hasil menunjukkan bahwa kalkon A, B, dan C telah berhasil disintesis dengan metode sonokimia dengan rendemen sebesar 81, 67, dan 79%. Siklisasi kalkon dengan metode konvensional menghasilkan pirazolina A, B, dan C dengan rendemen sebesar 75, 63, dan 74%. Metode sonokimia gagal menghasilkan pirazolina A tetapi berhasil menghasilkan pirazolina B and C dengan rendemen sebesar 20 dan 58%. Uji sitotoksisitas pirazolina menunjukkan bahwa pirazolina C memiliki sitotoksisitas tinggi terhadap sel kanker HeLa, MCF-7, T47D dan WiDr namun toksik juga terhadap sel Vero.

Synthesis of N-phenyl pyrazoline derivatives from veratraldehyde and various acetophenone and its cytotoxicity test towards cancer cell HeLa, MCF-7, T47D, WiDr have been done. The synthesis of N-phenyl pyrazoline was carried out in two-step reactions, i.e., cross aldol condensation (Claisen-Schmidt), and cyclocondensation while the cytotoxicity test of pyrazoline against several cancer cell lines and normal cell (Vero) was conducted by 3-(4,5-dimethylthiazole-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay. The aldol condensation was performed by reacting the mixture of veratraldehyde with acetophenone, 2-hydroxyacetophenone, 4-hydroxyaceto-phenone in ethanol in the presence of NaOH 40% as a catalyst using sonochemistry method to give 1-phenyl-3-(3',4'-dimethoxyphenyl)-2-propen-1-one (chalcone A), 1-(2'-hydroxyphenyl)-3-(3',4'-dimethoxyphenyl)-2-propen-1-one (chalcone B) dan 1-(4'-hydroxyphenyl)-3-(3',4'-dimethoxyphenyl)-2-propen-1-one (chalcone C). The cyclization of chalcone with phenylhydrazine was carried out with conventional and sonochemistry methods to yield 1-phenyl-3-(phenyl)-5-(3',4'-dimethoxyphenyl)-2-pyrazoline (pyrazoline A), 1-phenyl-3-(2'-hydroxyphenyl)-5-(3',4'-dimethoxyphenyl)-2-pyrazoline (pyrazoline B), 1-phenyl-3-(4'-hydroxyphenyl)-5-(3',4'-dimethoxyphenyl)-2-pyrazoline (pyrazoline C). All of the products were elucidated using FT-IR, GC-MS, 1H- dan 13C-NMR spectrometers. The result showed that chalcone A, B, and C had been successfully synthesized by sonochemistry method in 81, 67, and 79% yields. Cyclization of chalcone by conventional methods yielded pyrazoline A, B, and C in 75, 63, and 74%, respectively. Unfortunately, the sonochemistry method failed to give pyrazoline A, but pyrazoline B and C produced in 20 and 58% yield. Cytotoxicity test of pyrazoline showed that pyrazoline C has high cytotoxicity towards cancer cells HeLa, MCF-7, T47D, and WiDr but also toxic towards Vero cell.

Kata Kunci : N-fenil pirazolina, antikanker, MTT, kalkon/ N-phenylpyrazoline, anticancer, MTT assay, chalcone

  1. S2-2018-388447-abstract.pdf  
  2. S2-2018-388447-bibliography.pdf  
  3. S2-2018-388447-tableofcontent.pdf  
  4. S2-2018-388447-title.pdf