Penentuan Analog Kurkumin Terbaik dari 5-Bromo-2-Hidroksibenzaldehida melalui Penambatan Molekul pada Protein Plasmodium falciparum Lactate Dehydrogenase (PfLDH) dan Sarco/endoplasmic Reticulum Ca2+-ATPase (SERCA), Sintesis serta Uji Aktivitas sebagai Antimalaria

DYAH AYUNING S, Dr. Endang Astuti, M.Si.;Dr. Deni Pranowo, S.Si, M.Si.

2022 | Skripsi | S1 KIMIA

Penelitian ini bertujuan untuk mengetahui pengaruh penambahan gugus bromo pada senyawa analog kurkumin dengan variasi keton berupa aseton (1,5-bis(5-bromo-2-hidroksibenzilidin)penta-1,4-dien-3-on/analog kurkumin A), siklopentanon (2,5-bis(5-bromo-2-hidroksibenzilidin)siklopentanon/analog kurkumin B), dan sikloheksanon (2,6-bis(5-bromo-2-hidroksibenzilidin)sikloheksanon/analog kurkumin C) terhadap aktivitas antimalaria melalui penambatan molekul pada protein PfLDH dan SERCA dengan PDB ID: 1U4O dan 2EAU menggunakan software AutoDock Vina 1.1.2. Sintesis analog kurkumin C dengan interaksi terbaik dari 5-bromo-2-hidroksibenzaldehida dan sikloheksanon dalam etanol menggunakan katalis NaOH. Senyawa prekursor 5-bromo-2-hidroksibenzaldehida diperoleh dari reaksi 2-hidroksibenzaldehida dengan KBrO3, HBr 47%, dan asam asetat glasial. Karakterisasi analog kurkumin C dilakukan dengan FTIR, DI-MS/MS, 1H-NMR, dan analisis elemental. Uji aktivitas antimalaria secara in vitro dilakukan terhadap parasit P. falciparum strain FCR-3. Hasil penelitian menunjukkan adanya penambahan gugus bromo pada analog kurkumin C dapat meningkatkan aktivitas pada residu asam amino protein PfLDH berupa Met30, Ile31, Ser245, dan Thr97 dengan nilai afinitas ikatan -8,1 kkal mol-1 serta protein SERCA pada residu asam amino Gln56, Gln108, dan Asp59 dengan nilai afinitas ikatan -9,0 kkal mol-1. Senyawa analog kurkumin C berhasil disintesis berupa padatan berwarna oranye dengan rendemen sebesar 34,78%. Senyawa analog kurkumin C terbukti sangat aktif sebagai antimalaria dengan nilai IC50 1,83 μg/mL dibandingkan senyawa kurkumin dengan nilai IC50 6,51 μg/mL pada uji in vitro terhadap P. falciparum strain FCR-3.

This study aims to determine the effect of bromo group substituted curcumin analogue compounds with ketone variations in the form of acetone (1,5-bis(5-bromo-2-hydroxybenzylidine)penta-1,4-dien-3-one/curcumin analogue A), cyclopentanone (2,5-bis(5-bromo-2-hydroxybenzylidine)cyclopentanone/curcumin analogue B), and cyclohexanone (2,6-bis(5-bromo-2-hydroxybenzylidine)cyclohexanone/curcumin analogue C) against PfLDH and SERCA proteins as antimalarial through molecular docking with PDB ID: 1U4O and 2EAU using AutoDock Vina 1.1.2 software. Synthesis of curcumin analogue C with the best interaction from 5-bromo-2-hydroxybenzaldehyde and cyclohexanone in ethanol using NaOH catalyst. The precursor compound 5-bromo-2-hydroxybenzaldehyde was obtained from the reaction of 2-hydroxybenzaldehyde with KBrO3, HBr 47%, and glacial acetic acid. The characterization of curcumin analogue C was carried out by FTIR, DI-MS/MS, 1H-NMR, and elemental analysis. Antimalarial activity test using in vitro against P. falciparum strain FCR-3 parasite. The results of this research showed that the bromo group substituted curcumin analogue C could increase the activity on amino acid residues of PfLDH protein in the form of Met30, Ile31, Ser245, and Thr97 has binding affinity value of -8.1 kcal mol-1 and SERCA protein on amino acid residues Gln56, Gln108, and Asp59 with binding affinity value of -9.0 kcal mol-1. Curcumin analogue C compound has been successfully synthesized to produce orange solid with yield of 34.78%. Curcumin analogue C compound proved to be very active as an antimalarial compound and its IC50 was 1.83 g/mL compared to curcumin compound with IC50 value of 6.51 g/mL by in vitro test against P. falciparum strain FCR-3.

Kata Kunci : analog kurkumin, antimalaria, penambatan molekul, PfLDH, SERCA.