PENAMBATAN MOLEKULER, SINTESIS, DAN UJI AKTIVITAS SENYAWA ANALOG KURKUMIN MONOKARBONIL BERBAHAN DASAR 3-HIDROKSIBENZALDEHIDA DENGAN VARIASI KETON TERHADAP ENZIM PfLDH SEBAGAI ANTIMALARIA

ZUHDI URBANNINGRUM, Dr. Endang Astuti, M.Si; Dr. Deni Pranowo, M.Si

2022 | Skripsi | S1 KIMIA

Penelitian penambatan molekuler, sintesis dan uji aktivitas senyawa analog kurkumin monokarbonil berbahan dasar 3-hidroksibenzaldehida dengan variasi keton terhadap enzim PfLDH sebagai antimalaria telah berhasil dilakukan. Penambatan molekuler senyawa analog kurkumin A-F terhadap enzim PfLDH (PDB ID: 1CET) dilakukan dengan tujuan untuk mengetahui nilai afinitas ikatan dan interaksi yang terjadi. Senyawa analog kurkumin dengan nilai afinitas ikatan paling besar dan membentuk interaksi spesifik dari hasil penambatan molekuler, dilakukan sintesis menggunakan metode kondensasi Claisen-Schmidt dengan mereaksikan 3-hidroksibenzaldehida dan satu varian keton menggunakan katalis NaOH. Produk sintesis selanjutnya dikarakterisasi dengan spektrofotometer FT-IR, spektrometer MS/MS, spektrometer 1H-NMR dan 13C-NMR. Uji aktivitas antimalaria senyawa analog kurkumin hasil sintesis dan kurkumin dilakukan secara in vitro terhadap Plasmodium falciparum strain FCR-3. Hasil penelitian diperoleh nilai afinitas ikatan senyawa analog kurkumin A-F dan kurkumin terhadap enzim PfLDH secara berurutan sebesar -6,40; -7,48; -7,82; -7,74; -7,96; -8,86; dan -6,53 kkal/mol. Berdasarkan hasil penambatan molekuler diketahui senyawa analog kurkumin F merupakan senyawa kandidat terbaik karena memiliki nilai afinitas ikatan paling besar dan interaksi spesifik dengan sisi aktif enzim PfLDH. Senyawa analog kurkumin F disintesis dengan kondensasi Clasien-Schmidt menghasilkan rendemen sebesar 71,9% dan kemurnian 100%. Pengujian aktivitas antimalaria senyawa analog kurkumin F terhadap P. falciparum strain FCR-3 sangat aktif dengan nilai IC50 sebesar 0,851 µM.

The experiment of molecular docking, synthesis, and activity test of 3-hydroxybenzaldehyde based monocarbonyl curcumin analog compound with ketone variations on PfLDH enzyme as an antimalarial had been carried out. Molecular docking of A-F curcumin analog compounds with PfLDH enzyme (PDB ID: 1CET) was carried out to determine the value of the binding affinity and the interactions. The curcumin analog compound with the best binding affinity and interaction from the molecular docking was synthesized using the Claisen-Schmidt condensation method by reacting 3-hydroxybenzaldehyde and one of the ketone variants using a NaOH catalyst. The synthesized product was further characterized by FT-IR spectrophotometer, MS/MS spectrometer, 1H-NMR spectrometer, and 13C-NMR. Antimalarial activity tests of synthetic curcumin analog compounds and curcumin were conducted in vitro against Plasmodium falciparum strain FCR-3. The results showed that the binding affinity of curcumin analogue compounds A-F and curcumin to PfLDH enzyme respectively was -6.40; -7.48; -7.82; -7.74; -7.96; -8.86; and -6.53 kcal/mol. Based on the results of molecular docking, it was found that F curcumin analogue were the best candidate compound which were indicated by the highest binding affinity values and had specific interactions with the active site of PfLDH enzyme. The analogue compound of curcumin F was synthesized by Clasien-Schmidt condensation obtained 71.9% yield and 100% purity. Testing the antimalarial activity of curcumin F analogue compounds against P. falciparum strain FCR-3 was very active with an IC50 of 0.851 µM.

Kata Kunci : 3-hidroksibenzaldehida, analog kurkumin, antimalaria, penambatan molekuler, PfLDH