SINTESIS ANALOG MONOKARBONIL KURKUMIN ASIMETRIS DAN PREDIKSI AKTIVITASNYA SEBAGAI ANTIMALARIA MELALUI PENAMBATAN MOLEKUL

AISYAH MUMTAZIYAH, Drs. Bambang Purwono, M.Sc., Ph.D.; Dra. Tutik Dwi Wahyuningsih M.Si., Ph.D.

2022 | Skripsi | S1 KIMIA

Penelitian sintesis analog monokarbonil kurkumin asimetris dan prediksi aktivitas antimalaria melalui penambatan molekul telah dilakukan. Penelitian ini bertujuan melakukan sintesis dua senyawa analog monokarbonil kurkumin asimetris dan mengetahui aktifitas antimalaria dari hasil penambatan molekuler terhadap Plasmodium falciparum DHFR-TS. Senyawa analog monokarbonil kurkumin asimetris diperoleh dari kondensasi Claisen-Schmidt senyawa benzalaseton A dan B dengan benzaldehida dan veratraldehida dengan penambahan katalis NaOH 10% melalui metode pengadukan yang menghasilkan produk (1E,4E)-1-(4-hidroksi-3-metoksifenil)-5-fenilpenta-1,4-dien-3-on (AMKA A) dan (1E,4E)-1-(3,4-dimetoksifenil)-5-(2-hidroksi-3-metoksifenil) penta-1,4-dien-3-on (AMKA B). Benzalaseton A ((E)-4-(4-hidroksi-3-metoksifenil)-but-3-en-2-on) disintesis dari reaksi kondensasi Claisen-Schmidt vanillin dengan aseton menggunakan katalis NaOH 8% sedang benzalaseton B (E)-4-(2-hidroksi-3-metoksifenil)-but-3-en-2-on disintesis dari reaksi kondensasi Claisen-Schmidt o-vanillin dengan aseton menggunakan katalis NaOH 8%. Elusidasi struktur produk dilakukan menggunakan spektrometer FTIR, GC-MS, LC-MS/MS, ¹H NMR dan ¹³C-NMR. Uji aktivitas antimalaria dilakukan dengan metode penambatan molekul untuk mengkaji afinitas ikatan dan interaksi senyawa terhadap protein PfDHFR-TS menggunakan software Autodock4. Sintesis senyawa benzalaseton A, benzalaseton B, AMKA A dan AMKA B menghasilkan produk dengan rendemen 71,8, 61,5, 91,2, dan 47,1%. Hasil penambatan molekul benzalaseton A dan B memberikan afinitas ikatan antara protein-ligan sebesar -5,51 dan -5,87 kkal/mol yang kurang stabil dari ligan alami. Senyawa AMKA A dan AMKA B menunjukkan ikatan stabil dengan protein PfDHFR-TS resisten serta memberikan afinitas ikatan sebesar -7,30 dan -8,22 kkal/mol yang berinteraksi spesifik dengan asam amino Asp54, Leu164, Cys15, dan Ala16 melalui ikatan hidrogen. Senyawa AMKA A dan AMKA B menujukkan kenaikkan aktivitas antimalaria dibandingkan kurkumin.

The experiment of asymmetric monocarbonyl curcumin analogues synthesis dan their antimalarial activity prediction through molecular docking had been carried out. The study aimed to synthesize two asymmetric monocarbonyl analogue compounds of curcumin and to determine the antimalarial activity of the molecular docking to Plasmodium falciparum DHFR-TS. The asymmetric monocarbonyl analogue of curcumin was obtained from the Claisen-Schmidt condensation of benzalacetone compounds A and B with benzaldehyde and veratraldehyde with the addition of 10% NaOH catalyst through stirring method, which resulted in the product (1E,4E)-1-(4-hydroxy-3-methoxyphenyl)- 5-phenylpenta-1,4-diene-3-one (AMKA A) and (1E,4E)-1-(3,4-dimethoxyphenyl)-5-(2-hydroxy-3-methoxyphenyl) penta-1,4 -dien-3-on (AMKA B). Benzalacetone A ((E)-4-(4-hydroxy-3-methoxyphenyl)-but-3-en-2-one) was synthesized from the Claisen-Schmidt vanillin condensation reaction with acetone using 8% NaOH as a catalyst while benzalacetone B (E)-4-(2-hydroxy-3-methoxyphenyl)-but-3-en-2-one was synthesized from the condensation reaction of Claisen-Schmidt o-vanillin with acetone using 8% NaOH as a catalyst. The structure elucidation of the product was carried out using FTIR, GC-MS, LC-MS/MS, ¹H-NMR, and ¹³C-NMR spectrometers. The antimalarial activity test was carried out using the molecular docking method to assess the binding affinity and interaction of the compound to the PfDHFR-TS protein using Autodock4 software. The results showed that the yield of benzalacetone A, benzalacetone B, AMKA A and AMKA B were 71.8, 61.5, 91.2, and 47.1% respectively. Benzalacetone A and B compounds gave binding affinities between protein-ligands of -5.51 and -5.87 kcal/mol, which were less stable than natural ligands. AMKA A and B compounds bind stably to resistant PfDHFR-TS protein by providing binding affinities of -7.30 and -8.22 kcal/mol, which interact specifically with amino acids Asp54, Leu164, Cys15, and Ala16 through hydrogen bonds. The compounds AMKA A and AMKA B showed an enhancement in antimalarial activity compared to curcumin.

Kata Kunci : AMKA, antimalaria, penambatan molekul