SINTESIS ANALOG KURKUMIN MONOKETON BERBAHAN DASAR BENZILOKSIBENZALDEHIDA DAN AKTIVITASNYA SEBAGAI INHIBITOR TERHADAP ALFA-AMILASE

MUHAMMAD BADRUL HUDA, Dr. Endang Astuti; Tri Joko Raharjo, M.Si., Ph.D

2020 | Tesis | MAGISTER KIMIA

Sintesis analog kurkumin monoketon berbahan dasar benziloksibenzaldehida, uji aktivitasnya sebagai inhibitor dan molecular docking terhadap enzim α-amilase telah dilakukan. Sintesis bahan dasar benziloksibenzaldehida dilakukan melalui reaksi eterifikasi Williamson pada senyawa hidroksibenzaldehida menggunakan pelarut DMF, K2CO3 sebagai basa, KI dan benzil klorida. Sintesis senyawa analog kurkumin dilakukan dengan reaksi Claisen-Schmidt antara dua jenis benziloksibenzaldehida yaitu 3-benziloksi-benzaldehida dan 4-benziloksibenzaldehida dengan tiga jenis keton yaitu aseton, siklopentanon dan sikloheksanon sehingga menghasilkan (1E,4E)-1,5-bis(3-(benziloksi)fenil)-1,4-pentadien-3-on (analog kurkumin A), (2E,5E)-2,5-bis(3-(benziloksi)benzilidin)siklopentanon (analog kurkumin B), (2E,6E)-2,6-bis(3-(benziloksi)benzilidin)sikloheksanon (analog kurkumin C), (1E,4E)-1,5-bis(4-(benziloksi)fenil)-1,4-pentadien-3-on (analog kurkumin D), (2E,5E)-2,5-bis(4-(benziloksi)benzilidin)siklopentanon (analog kurkumin E), (2E,6E)-2,6-bis(4-(benziloksi)benzilidin)sikloheksanon (analog kurkumin F). Hasil sintesis dianalisis strukturnya menggunakan spektrometer FTIR, LCMS/MS, 1H- dan 13C-NMR. Senyawa analog kurkumin dan akarbosa sebagai pembanding dilakukan uji aktivitas inhibisi terhadap enzim α-amilase serta ditentukan tipe inhibitornya. Molecular docking dilakukan untuk mengetahui jenis interaksi dan afinitas ikatan senyawa hasil sintesis dengan enzim α-amilase. Hasil penelitian diperoleh 3-benziloksibenzaldehida dan 4-benziloksi-benzaldehida masing-masing menghasilkan yield sebesar 90,2 dan 88,8%. Sintesis analog kurkumin A, B, C, D, E dan F masing-masing menghasilkan yield sebesar 89,7; 97,4; 94,6; 97,3; 93,2 dan 78,1%. Uji aktivitas inhibisi menunjukkan empat senyawa analog kurkumin hasil sintesis memiliki aktivitas inhibisi lebih tinggi dari pada akarbosa yaitu senyawa analog kurkumin C, D, E dan F dengan nilai IC50 masing-masing senyawa adalah 28,84; 19,05; 16,98 dan 19,95 µM. Senyawa analog kurkumin A dan B memiliki aktivitas inhibisi yang lebih rendah dari pada akarbosa dengan nilai IC50 sebesar 33,11 dan 37,15 µM. Senyawa akarbosa memiliki nilai IC50 sebesar 32,35 µM. Senyawa Analog kurkumin A, B, C, D, E, F dan akarbosa memiliki tipe penghambatan unkompetitif terhadap enzim α-amilase. Molecular docking senyawa analog kurkumin terhadap enzim α-amilase menunjukkan senyawa analog kurkumin A, B, C, D, E, dan F memiliki afinitas ikatan yang lebih rendah dari pada senyawa akarbosa.

Synthesis of monoketone curcumin analogs from benzyloxybenzaldehyde, testing of its activity as inhibitor and molecular docking an α-amylase enzyme has been carried out. The synthesis of benzyloxybenzaldehyde base material was carried out through the Williamson etherification reaction on the hydroxybenzaldehyde compound using DMF as a solvent, K2CO3 as a base, KI and benzyl chloride. The synthesis of curcumin analogs compounds was conducted through the Claisen-Schmidt reaction between two types of benzyloksibenzaldehide (3-benzyloksibenzaldehyde and 4-benzyloksi-benzaldehyde) with three types of ketones (acetone, cyclopentanon and cyclohexanone) to produce (1E, 4E)-1,5-bis(3-benzyloxy))phenyl)-1,4-pentadient-3-one (curcumin analog A), (2E, 5E)-2,5-bis (3-(benzyloxy)benzylidine)cyclopentanone (curcumin analog B), (2E, 6E)-2,6-bis (3-(benzyloxy)benzylidine) cyclohexanone (curcumin analog C), (1E, 4E)-1,5-bis(4-(benzyloxy)phenyl)-1,4-pentadient-3-on (curcumin analog D), (2E, 5E)-2,5-bis(4-(benzyloxy)benzylidine)cyclopentanone (curcumin analog E), (2E, 6E)-2,6-bis (4-(benzyloxy)benzylidine))cyclohexanone (curcumin analog F). Furthermore, the results of the synthesis were analyzed using FTIR, LCMS/MS, 1H- and 13C-NMR spectrometers. The obtained curcumin analog was tested for its inhibitory activity against the α-amylase enzyme and determined the type of inhibitor. The inhibitory activity test of the α-amylase enzyme was also carried out on the acarbose as a comparison. Molecular docking was carried out to find out the type of interaction and the affinity of the bonds of the synthesized compound with the α-amylase enzyme. The results showed that 3-benzyloxybenzaldehyde and 4-benzyloxy-benzaldehyde produced yields of 90.2 and 88.8%, respectively. Synthesis of curcumin analogs A, B, C, D, E and F yielded of 89.7; 97.4; 94.6; 97.3; 93.2 and 78.1%, respectively. The inhibitory activity of four curcumin analog compounds (C, D, E dan F) were higher that of the acarbose. On the contrary, the inhibitory activity of analog A and B was lower that of the acarbose. Curcumin analog compounds (A, B, C, D, E, and F) and acarbose have an uncompetitive inhibitory type of the α-amylase enzyme. Molecular docking study revealed that the curcumin analog compounds have lower binding affinity than that of acarbose.

Kata Kunci : curcumin analogs, α-amylase, benzyloxybenzaldehyde, docking