Sintesis Analog Kurkumin Simetris dari Turunan Hidroksibenzaldehida dan Uji Aktivitasnya sebagai Inhibitor Enzim Alfa-Amilase serta Efek Sinergisitasnya dengan Asam Ferulat

LESTY MEITIKA, Prof. Dr. Chairil Anwar, Dr. Tutik Dwi Wahyuningsih, M.Si.

2019 | Tesis | MAGISTER KIMIA

Senyawa 2,6-bis(4-hidroksi-3-metoksibenzilidin)sikloheksanon (analog kurkumin A), senyawa 2,6-bis(4-hidroksibenzilidin)sikloheksanon (analog kurkumin B), dan senyawa 2,6-bis(3-hidroksibenzilidin)sikloheksanon (analog kurkumin C) telah berhasil disintesis. Uji aktivitas senyawa analog kurkumin A, B, dan C sebagai inhibitor enzim alfa-amilase dan efek sinergisitasnya dengan asam ferulat telah dilakukan. Sintesis senyawa analog kurkumin berlangsung melalui reaksi Claisen-Schmidt antara turunan hidroksibenzaldehida (vanilin, 4-hidroksi benzaldehida, dan 3-hidroksibenzaldehida) dengan sikloheksanon dalam suasana asam. Struktur senyawa hasil sintesis dikonfirmasi dengan Spektrofotometer FTIR, Direct Inlet-MS, Spektrometer 1H- dan 13C-NMR. Hasil penelitian diperoleh analog kurkumin A berupa padatan berwarna kuning dengan rendemen 65,03% dan titik leleh 178-179 °C, analog kurkumin B berupa padatan berwarna hijau pucat dengan rendemen 67,35% dan titik leleh 288-289 °C, dan analog kurkumin C berupa padatan berwarna oranye dengan rendemen 66,34% dan titik leleh 211-213 °C. Senyawa analog kurkumin A, B, dan C berpotensi sebagai inhibitor enzim alfa-amilase dengan aktivitas inhibisi tertinggi masing-masing 32,52; 87,69; dan 69,30% pada konsentrasi 1 mM dengan nilai IC50 12,14; 2,54 dan 3,73 mM. Senyawa analog kurkumin B memiliki aktivitas inihibisi terbaik 87,69% dan nilai IC50 2,54 mM. Uji sinergisitas menunjukkan bahwa kombinasi senyawa analog kurkumin A dan asam ferulat dengan perbandingan 1:1 memberikan efek sinergis ringan-sedang dengan nilai IC50 sebesar 2,43 mM. Kombinasi senyawa analog kurkumin B dan asam ferulat memberikan aktivitas inhibisi optimum pada perbandingan 2:1 dengan nilai IC50 sebesar 1,27 mM dan menghasilkan efek sinergis ringan-sedang. Kombinasi senyawa analog kurkumin C pada semua perbandingan memberikan efek antagonis.

Compounds of 2,6-bis(4-hydroxy-3-methoxybenzylidene)cyclohexanone (curcumin analogue A), 2,6-bis(4-hydroxybenzylidene)cyclohexanone (curcumin analogue B), and 2,6-bis(3-hydroxybenzylidene)cyclohexanone (curcumin analogue C) have been successfully synthesized. Activity assay of curcumin analogues A, B, and C as inhibitor alpha-amylase enzyme and synergism effect with ferulic acid have also been carried out. The synthesis of curcumin analogues has been performed through Claisen-Schmidt reaction between hydroxybenzaldehyde derivatives (vanillin, 4-hydroxybenzaldehyde, and 3-hydroxybenzaldehyde) and cyclohexanone in acid condition. The structures of the products were elucidated by FTIR Spectrophotometer, Direct Inlet-Mass Spectrometer, 1H-, and 13C-NMR Spectrometer. The results showed that curcumin analogue A was obtained as yellow solid in 65.03% yield with m.p. of 178-179 °C, curcumin analogue B was yielded as pale green solid in 67.35% with m.p. of 288-289 °C and curcumin analogue C was produced in 66.34% as orange solid with m.p. of 211-213 °C. The results of inhibition activities of alpha-amylase enzyme showed that curcumin analogues A, B, and C were potential as an alpha-amylase enzyme inhibitor with the inhibition activity at concentration 1 mM of 32.52; 87.69; and 69.30% and IC50 of 12.31; 2.54; and 3.73 mM respectively. Curcumin analogue B was the best inhibitor alpha-amylase enzyme with inhibition activity of 87.69% and IC50 of 2.54 mM. The results of the synergistic assay showed that the combination of curcumin analogue A and ferulic acid (1:1) indicates a moderate to slight synergism effect with IC50 of 2.43 mM. The combination of curcumin analogue B and ferulic acid (2:1) had the optimum of inhibition activity with IC50 of 1.27 mM and gave a moderate to slight synergism effect. The combination of curcumin analogue C had an antagonism effect in all concentration ratios.

Kata Kunci : analog kurkumin, antidiabetes, enzim alfa-amilase, asam ferulat