SINTESIS SENYAWA TURUNAN PIRAZOLINA DENGAN PREKURSOR p-ANISALDEHIDA DAN 2-HIDROKSIASETOFENON SERTA UJI SITOTOKSISITASNYA TERHADAP BEBERAPA SEL KANKER

DINA NUR SHINTA, Dr. Tutik Dwi Wahyuningsih, M.Si.; Sugeng Triono, S.Si., M.Si.

2017 | Skripsi | S1 KIMIA

Sintesis senyawa turunan pirazolina dan uji sitotoksisitasnya terhadap beberapa sel kanker telah dilakukan. Penelitian ini bertujuan untuk mensintesis 1-(2-hidroksifenil)-3-(4- metoksifenil)-2-propen-1-on (kalkon) dari p-anisaldehyde and 2-hidroksiasetofenon, mensintesis 1-(5-(4-metoksifenil)-3-(2-hidroksifenil)-4,5-dihidro-1H-pirazol-1il)etanon (pirazolina 1) dari kalkon dan hidrazin hidrat dengan adanya asam asetat glasial, melakukan sintesis senyawa N-fenil-3-(2-hidroksifenil)-5-(4-metoksifenil)-2-pirazolina (pirazolina 2) serta melakukan uji sitotoksisitas untuk menentukan nilai IC50 senyawa pirazolina 2 hasil sintesis terhadap sel kanker WiDr dan T47D. Sintesis diawali dengan mereaksikan 2-hidroksiasetofenon dan p-anisaldehida dalam suasana basa KOH menghasilkan senyawa turunan kalkon melalui reaksi kondensasi Claisen-Schmidt. Hidrazin hidrat ditambahkan secara bertetes-tetes ke dalam larutan kalkon dengan metode refluks. Penambahan selanjutnya dengan asam asetat glasial menghasilkan pirazolina 1. Pirazolina 2 diperoleh melalui penambahan fenilhidrazin ke dalam larutan kalkon menggunakan metode refluks maupun sonokimia selama 7 jam. Struktur produk dielusidasi dengan menggunakan spektrometer FT-IR, GC-MS, 1H- and 13C-NMR. Uji sitotoksisitas pirazolina 2 dilakukan terhadap T47D dan WiDr menggunakan metode MTT untuk menentukan nilai IC50. Senyawa kalkon yang diperoleh berupa padatan kuning terang dengan persen hasil 73,39%. Pirazolina 1 didapatkan dengan warna putih dengan persen hasil 1,29%, sedangkan Pirazolina 2 dihasilkan sebagai padatan putih dengan persen hasil 77,00% melalui metode sonokimia dan 52,90% melalui metode refluks. Pirazolina 2 diuji aktivitas biologinya sebagai senyawa antikanker. Nilai IC50 terhadap T47D dan WiDr secara berturut-turut yaitu 255,94 and 416,87 μg/mL. Berdasarkan hasil tersebut, pirazolina 2 tidak memberikan toksisitas yang signifikan terhadap sel kanker T47D dan WiDr.

Synthesis and anticancer activity assay of pyrazoline derivatives have been done. The aim of this research were to synthesize 1-(2-hydroxyphenyl)-3-(4- methoxyphenyl)-2-propen-1-one (chalcone) from p-anisaldehyde and 2-hydroxyacetophenone, to synthesize 1-(5-(4-methoxyphenyl)-3-(2-hydroxyphenyl)-4,5-dihydro-1H-pyrazol-1-yl)etanone (pyrazoline 1) from chalcone and hydrazine hydrate in glacial acetic acid, to synthesize N-phenyl-3-(2-hydroxyphenyl)-5-(4-methoxyphenyl-2-pyrazoline (pyrazoline 2) and to determine the cytotoxicity of pyrazoline against several cancer cell lines. The synthesis was started by reacting 2-hydroxyacetophenone and p-anisaldehyde in the presence of KOH to give chalcone via Claisen-Schmidt condentation. Hydrazine hydrate was added dropwise into solution of chalcone in methanol under reflux temperature. Further addition of glacial acetic acid into reaction mixture would produce pyrazoline 1. In addition, Pyrazoline 2 was obtained by adding phenylhydrazine to chalcone in methanol. The mixture was irradiated in ultrasonic bath or reacted under reflux for 7 hours. The structures were elucidated by FT-IR, GC-MS, 1H- and 13C-NMR analysis. The pyrazoline 2 cytotoxicity was tested against T47D and WiDr cells by MTT method to determine the IC50 value. The chalcone was obtained as bright yellow solid and in 73.39% yield. Pyrazoline 1 was produced as white solid in 1.29% yield, respectively, while pyrazoline 2 was yielded as broken white solid in 77.00% by sonochemistry and 52.90% by reflux method. Pyrazoline 2 was tested for their biological activity as anticancer. The IC50 value againts T47D, and WiDr cells were 255.94 and 416.87 μg/mL. Respectively, it was concluded that the pyrazoline 2 showed no-significant anticancer activity.

Kata Kunci : kalkon, pirazolina, sonokimia, sitotoksisitas/chalcone, pyrazoline, sonochemistry, citotoxicity