SINTESIS DAN UJI AKTIVITAS ANTIMALARIA ANALOG KURKUMIN DARI 2-METOKSIBENZALDEHIDA DENGAN VARIASI KETON SERTA PENAMBATAN MOLEKUL TERHADAP PROTEIN PfLDH

MUHAMMAD AFIN AL BASYAR, Prof. Dr.rer.nat. Harno Dwi Pranowo, M.Si ; Dr. Endang Astuti, M.Si

2021 | Skripsi | S1 KIMIA

Telah dilakukan penelitian sintesis dan uji aktivitas antimalaria analog kurkumin hasil sintesis 2-metoksibenzaldehida dengan variasi keton serta penambatan molekul terhadap protein PfLDH. Penelitian ini bertujuan untuk melakukan sintesis senyawa analog kurkumin dari 2-metoksibenzaldehida dengan aseton, siklopentanon, sikloheksanon menggunakan katalis basa, mengetahui aktivitas senyawa analog kurkumin hasil sintesis dan kurkumin sebagai antimalaria secara in vitro dengan uji antiplasmodium terhadap P. falciparum strain FCR3, dan mengetahui nilai energi afinitas ikatan yang terbentuk antara senyawa analog kurkumin dan kurkumin dengan sisi aktif enzim PfLDH menggunakan uji in silico metode penambatan molekul. Sintesis dilakukan dengan bahan awal 2-metoksibenzaldehida dalam etanol dengan aseton (analog kurkumin A), siklopentanon (analog kurkumin B), sikloheksanon (analog kurkumin C). Reaksi ini menggunakan katalis NaOH. Campuran tersebut diaduk selama 24 jam pada suhu ruang. Larutan dinetralisasi dengan HCl 37% hingga pH 6-7 dan terbentuk padatan. Padatan difiltrasi dan direkristalisasi menggunakan etanol. Produk hasil sintesis diidentifikasi dengan KLT, spektrofotometer FT-IR, spektrometer 1H-NMR, 13C-NMR, spektrometer DI-MS, dan LC-MS. Uji aktivitas antimalaria dilakukan dengan metode in vitro menggunakan parasit Plasmodium falciparum strain FCR3 dan studi interaksi dilakukan dengan metode penambatan molekul terhadap protein PfLDH. Hasil penelitian diperoleh senyawa analog kurkumin (1E,4E)-1,5-bis(2-metoksifenil)-1,4-pentadiena-3-on (analog kurkumin A), analog kurkumin (2E,5E)-2,5-bis(2-metoksibenzilidin)siklopentanon (analog kurkumin B), dan analog kurkumin (2E,6E)-2,6-bis(2- metoksibenzilidin)sikloheksanon (analog kurkumin C) dengan yield yang diperoleh dari hasil sintesis berurutan adalah 56,6%; 51,7%;dan 47,5%. Senyawa analog kurkumin A, B, dan C terbukti sangat aktif dalam uji in vitro terhadap P. falciparum strain FCR3 dengan nilai IC50 berurutan 1,09; 0,69;dan 2,01 µM. Senyawa analog kurkumin A, B, dan C berinteraksi stabil dengan protein reseptor PfLDH memberikan energi afinitas ikatan berurutan -5,47; -5,69;dan -4,60 kkal mol-1. Ketiga analog kurkumin berinteraksi spesifik dengan asam amino Arg171 melalui ikatan hidrogen.

Synthesis and antimalarial activity test of synthesized curcumin analogues from starting material 2-metoxybenzaldehyde using ketones variations with molecular docking on PfLDH protein has been carried out. The aims of this study were to synthesize curcumin analogue compounds from 2-methoxybenzaldehyde with acetone, cyclopentanone, cyclohexanone used base catalysts, to determine the activity of curcumin analog compounds produced and curcumin as antimalarials in vitro with antiplasmodium test against P. falciparum strain FCR3, and to determine the energy value of the bond affinity formed between curcumin and curcumin analog compounds with the active site of the PfLDH enzyme using in silico with method molecular docking. The synthesis analogue curcumines were carried out with the starting material 2-methoxybenzaldehyde in ethanol with acetone (analogue curcumin A), cyclopentanone (analogue curcumin B), cyclohexanone (analogue curcumin C). The reaction used NaOH as catalyst. The mixture is stirred for 24 hours at room temperature. The solution was neutralized with 37% HCl to pH 6-7 and a solid is formed. The solid was filtered and recrystallized using ethanol. The synthesized products were identified by TLC, FT-IR spectrophotometer, 1H-NMR spectrometer, 13C-NMR, DI-MS spectrometer, and LC-MS. The antimalarial activity test was carried out by in vitro method using the parasite P. falciparum strain FCR3 and interaction studies were carried out using the molecular docking method of PfLDH protein. The results showed curcumin analog compounds (1E, 4E)-1,5-bis(2-methoxyphenyl) -1,4-pentadiene-3-on (analogue curcumin A), curcumin analogue (2E, 5E)-2,5-bis(2-methoxybenzilidine) cyclopentanone (analogue curcumin B), and curcumin analogue (2E, 6E)-2,6-bis(2- methoxybenzilidine) cyclohexanone (analogue curcumin C) with the yield obtained from the synthesis results, respectively 56.6%, 51.7%, 47.5%. Curcumin analogue compounds A, B, and C proved to be very active in in vitro tests against P. falciparum strain FCR3 with a value of IC50, sequentially 1.09; 0.69; and 2.01 µM. Curcumin analogue compounds A, B, and C gived negative values for bond affinity energy when interacting with PfLDH protein, respectively -5.47; -5.69; and -4.60 kcal mol-1. The three curcumin analogues bonded specifically with the amino acid Arg171 through hydrogen bond.

Kata Kunci : antimalaria, penambatan molekul, senyawa analog kurkumin