AKTIVITAS ANTIMALARIA ANALOG KURKUMIN HASIL SINTESIS 2-HIDROKSIBENZALDEHIDA DENGAN VARIASI KETON DAN STUDI INTERAKSINYA TERHADAP PROTEIN SERCA
ILHAM SATRIA R P, Dr. Endang Astuti, M.Si; Tri Joko Raharjo, M.Si., Ph.D
2020 | Skripsi | S1 KIMIATelah dilakukan uji aktivitas antimalaria analog kurkumin hasil sintesis 2-hidroksibenzaldehida dengan variasi keton dan studi interaksinya terhadap protein SERCA. Penelitian ini bertujuan untuk melakukan sintesis senyawa analog kurkumin dari 2-hidroksibenzaldehida dengan aseton, siklopentanon, dan sikloheksanon, menguji secara in vitro terhadap P. falciparum strain 3D7 menggunakan senyawa analog kurkumin hasil sintesis, serta melakukan docking variasi senyawa hasil sintesis terhadap protein sarco/endoplasmic reticulum Ca2+-ATPase (SERCA) yang merupakan ortolog protein PfATP6. Senyawa 2-hidroksibenzaldehida dalam etanol ditambahkan dengan variasi keton dan NaOH. Campuran diaduk selama 24 jam pada suhu ruang. Hasil pengadukan ditambahkan dengan akuades dan dinetralkan dengan HCl. Padatan yang terbentuk difiltrasi dan direkristalisasi menggunakan metanol/etanol dan akuades. Produk yang diperoleh diidentifikasi menggunakan KLT, spektrofotometer FT-IR, spektrometer 1H-NMR dan 13C-NMR, serta spektrometer LC-MS/MS. Uji aktivitas antiplasmodium dilakukan secara in vitro terhadap parasit Plasmodium falciparum strain 3D7. Interaksi yang terjadi antara analog kurkumin hasil sintesis dengan parasit dipelajari menggunakan studi molecular docking terhadap protein SERCA dengan software Autodock4. Hasil penelitian diperoleh senyawa analog 1,5-bis(2-hidroksifenil)penta-1,4-dien-3-on (kurkumin A); 2,5-bis(2-hidroksibenzilidin)siklopentanon (kurkumin B); dan 2,6-bis(2-hidroksibenzilidin)sikloheksanon (kurkumin C) yang disintesis melalui reaksi Claisen-Schmidt dengan hasil berturut-turut sebesar 58,39; 87,06; dan 60,88 %. Uji in vitro analog kurkumin A, B, C, dan kontrol kurkumin terhadap P. falciparum strain 3D7 menghasilkan nilai IC50 berturut-turut sebesar 0,63; 0,04; 11,53; dan 7,84 µM. Studi interaksi terhadap protein SERCA diperoleh data afinitas ikatan analog kurkumin A, B, C, dan kontrol kurkumin masing-masing sebesar -7,52; -5,91; -5,52; dan -6,02 kkal mol-1. Berdasarkan hasil tersebut, kurkumin B mampu berinteraksi dengan stabil terhadap sisi aktif protein parasit dan sangat aktif menghambat parasit P. falciparum strain 3D7 sehingga berpotensi sebagai senyawa antimalaria.
Antimalarial activity of synthesized curcumin analogues from 2-hydroxybenzaldehyde using ketone variations and their interaction study on SERCA protein has been carried out. The purposes of this study were to synthesize the curcumin analog compound using 2-hydroxybenzaldehyde with acetone, cyclopentanone, and cyclohexanone, to test the compounds using in vitro against P. falciparum strain 3D7, and to perform docking analysis to the compounds against the sarco/endoplasmic reticulum Ca2+-ATPase (SERCA) protein which is an ortholog protein of PfATP6. The synthesis was started with gradually mixing of 2-hydroxybenzaldehyde to the ketones in ethanol. The mixture was then stirred for 24 hours at room temperature. The result was diluted with distilled water and neutralized with hydrochloric acid. The precipitant was filtered and recrystallized using methanol/ethanol and distilled water. The obtained products were identified using TLC, FT-IR spectrophotometer, 1H-NMR and 13C-NMR spectrophotometer, and LC-MS/MS spectrometers. In vitro antiplasmodium activity test was carried out against Plasmodium falciparum strain 3D7. The interactions between synthesized curcumin analogues on parasites were studied using molecular docking of SERCA proteins using Autodock4 software. The results showed that curcumin analogues compounds of 1,5-bis(2-hydroxyphenyl)penta-1,4-dien-3-one (curcumin A); 2,5-bis(2-hydroxybenzylidine) cyclopentanone (curcumin B); and 2,6-bis(2-hydroxybenzylidine)cyclohexanone (curcumin C) have been successfully synthesized with yield of 58.39; 87.06; and 60.88 %, respectively. The antimalarial activity of curcumin analogues A, B, C, and control curcumin compounds against P. falciparum strain 3D7 obtained the IC50 values of 0.63; 0.04; 11.53; and 7.84 µM. Interaction studies on the SERCA protein obtained that the binding affinity of curcumin analogues A, B, C, and control curcumin compounds are -7.52; -5.91; -5.52, and -6.02 kcal mol-1, respectively. Based on these results, curcumin B has the potential as an antimalarial compound because it is able to interact stably with the active side of the parasitic protein and could inhibit the P. falciparum strain 3D7 very actively.
Kata Kunci : aktivitas inhibisi, analog kurkumin, malaria, molecular docking, SERCA
