SINTESIS DAN UJI AKTIVITAS ANTIMALARIA SENYAWA TURUNAN KALKON DAN N-FENILPIRAZOLINA DARI BENZALDEHIDA DAN TURUNAN ASETOFENON

LU'LU'ATUL MAGHFIROH, Dr. Tutik Dwi Wahyuningsih, M.Si.; Dr. Endang Astuti, M.Si.

2019 | Tesis | MAGISTER KIMIA

Sintesis turunan N-fenilpirazolina berbahan dasar benzaldehida dan turunan asetofenon berupa n-asetofenon, 4-hidroksiasetofenon, 4-metoksiasetofenon serta uji aktivitasnya sebagai antimalaria dengan metode polimerisasi heme dan P. falciparum telah dilakukan. Penelitian diawali dengan sintesis kalkon dengan mereaksikan turunan asetofenon, benzaldehida, dan KOH dengan metode pengadukan dan sonokimia untuk menghasilkan 1,3-difenil- 2-propen-1-on (kalkon A), 1-(4-hidroksifenil)-3-fenil-2-propen-1-on (kalkon B), dan 1-(4-metoksifenil)-3-fenil-2-propen-1-on (kalkon C). Sintesis senyawa turunan N-fenilpirazolina dilakukan dengan cara siklokondensasi senyawa kalkon hasil sintesis dengan fenilhidrazin dan penambahan asam asetat glasial menggunakan metode refluks selama 6 jam untuk menghasilkan 1,3-5-trifenil- 2-pirazolina (pirazolina A), 1-fenil-3-(4-hidroksifenil)-5-fenil-2-pirazolina (pirazolina B), dan 1-fenil-3-(4-metoksifenil)-5-fenil-2-pirazolina (pirazolina C). Kebenaran struktur senyawa hasil sintesis dielusidasi struktur dengan spektrometer FTIR, GC-MS, 1H- dan 13C-NMR. Berdasarkan hasil penelitian diperoleh senyawa turunan kalkon berupa padatan kuning (kalkon A dan B) dan putih (kalkon C) dengan persen hasil berturut-turut sebesar 89,40; 80,35; dan 77,30%. Senyawa N-fenilpirazolina yang diperoleh berupa padatan kuning kecoklatan (pirazolina A dan B) dan putih kecoklatan (pirazolina C) dengan persen hasil masing-masing sebesar 79,31; 83,87; dan 78,12%. Uji penghambatan polimerisasi heme menghasilkan nilai IC50 kalkon A-C lebih rendah dibandingkan klorokuin difosfat sebagai kontrol positif. Senyawa pirazolina A dan B terbukti aktif pada penghambatan polimerisasi heme dengan nilai IC50 kurang dari 37,5 mM. Senyawa pirazolina A-C juga diuji aktivitasnya terhadap P. falciparum dan hanya diperoleh nilai IC50 senyawa pirazolina B yang tergolong sangat aktif sebagai antimalaria dalam menghambat pertumbuhan P. falciparum strain FCR3 dengan nilai IC50 < 5 µg/mL. Skema 1. Jalur sintesis turunan kalkon dan N-fenilpirazolina

Synthesis N-phenylpirazoline derivatives from benzaldehyde and acetophenone derivatives such as n-acetophenone, 4-hydroxyacetophenone, 4-metoxyacetophenone and the activity assay as an antimalarial using heme polymerization method and P. falciparum have been carried out. Chalcones was synthesized from benzaldehyde, acetophenone derivatives, and KOH by stirred method and sonochemical method to give 1,3-diphenyl-2-propen-1-one (chalcone A), 1-(4-hydroxyphenyl)-3-phenyl-2-propen-1-one (chalcone B), and 1-(4-methoxyphenyl)-3-phenyl-2-propen-1-one (chalcone C). Synthesis of N-phenylpyrazoline derivatives was carried out by cyclocondensation of chalcone with phenylhydrazine and the addition of glacial acetic acid by reflux method for 6 hours to yield 1,3-5-triphenyl-2-pyrazoline (pyrazoline A), 1-phenyl-3- (4-hydroxyphenyl) -5-phenyl-2-pyrazoline (pyrazoline B), and 1-phenyl-3- (4-methoxyphenyl) -5-phenyl-2-pyrazoline (pyrazoline C). The structure elucidations of product were confirmed by FTIR spectrophotometer, GC-MS, 1H-and 13C-NMR spectrometers. Based on the results, chalcones were obtained as yellow solids (chalcone A and B) and white (chalcone C) in 89.40; 80.35; and 77.30%, respectively. N-phenylalpyrazoline derivatives were obtained brownish yellow solids (pyrazoline A and B) and brownish white (pyrazoline C) in 79.31; 83.87; and 78.12%. The heme polymerization assay produced IC50 value of chalcone A-C showed lower activity than chloroquine diphosphate as positive control. It was proven that the pirazolina A and B compounds were active in inhibition of heme polymerization with IC50 value less than 37,5 mM. Pirazolina A-C was also tested for its activity against P. falciparum and only obtained IC50 value of pyrazolina B is the most active as antimalarial in inhibiting the growth of P. falciparum strain FCR3 IC50 < 5 µg/mL. Scheme 1. Synthetic pathway for chalcone and N-phenylpyrazoline derivatives

Kata Kunci : antimalaria, N-fenilpirazolina, kalkon