SINTESIS DAN UJI AKTIVITAS TURUNAN NITROFENILKALIKS[4]-2-METILRESORSINARENA SEBAGAI SENYAWA ANTIOKSIDAN DAN ANTIMALARIA SERTA PENAMBATAN MOLEKUL TERHADAP RESEPTOR PfLDH

SITI ASTIKA NISA, Prof. Drs. Jumina, Ph.D; Dr. M. Idham Darussalam M., M.Sc

2023 | Tesis | MAGISTER KIMIA

Sintesis, uji aktivitas dan penambatan molekul turunan nitrofenilkaliks[4]-2-metilresorsinarena sebagai senyawa antioksidan dan antimalaria telah dilakukan. Senyawa turunan kaliks[4]-2-metilresorsinarena disintesis dalam satu tahap reaksi melalui reaksi siklokondensasi dengan mereaksikan resorsinol dan aldehida aromatik, yaitu 2-nitrobenzaldehida, 3-nitrobenzaldehida dan 4-nitrobenzaldehida. Reaksi dilakukan dengan menggunakan metode refluks dalam pelarut etanol dan katalis asam klorida 37%. Senyawa hasil sintesis dikarakterisasi menggunakan spektrometer FTIR, 1H-NMR, 13C-NMR, dan LC-MS. Uji aktivitas antioksidan dilakukan dengan metode DPPH (2,2-difenil-1-pikrilhidrazil), sedangkan uji aktivitas antimalaria dilakukan secara in vitro terhadap Plasmodium falciparum 3D7. Studi penambatan molekul dilakukan menggunakan perangkat lunak Autodock Vina terhadap reseptor PfLDH. Hasil penelitian menunjukkan bahwa senyawa C-2-nitrofenilkaliks[4]-2-metilresorsinarena (2NK), C-3-nitrofenilkaliks[4]-2-metilresorsinarena (3NK) dan C-4-nitrofenilkaliks[4]-2-metilresorsinarena (4NK) telah berhasil disintesis. Senyawa 2NK, 3NK dan 4NK memiliki persen hasil berturut-turut sebesar 86,4; 78,6 dan 95,7%. Senyawa 2NK, 3NK dan 4NK memiliki aktivitas antioksidan dengan nilai IC50 116,10; 135,85 dan 93,76 µg/mL, sehingga senyawa 2NK dan 3NK dikategorikan moderat sedangkan senyawa 4NK dikategorikan kuat sebagai senyawa antioksidan. Uji aktivitas antimalaria terhadap 2NK, 3NK dan 4NK menghasilkan nilai IC50 berturut-turut 2,35; 1,68 dan 1,79 µM, sehingga senyawa-senyawa tersebut tergolong aktif sebagai antimalaria. Penambatan molekul yang dilakukan terhadap reseptor P. falciparum lactate dehydrogenase (PfLDH) menunjukkan bahwa senyawa 2NK, 3NK dan 4NK memiliki nilai afinitas ikatan berturut-turut -5,1; -6,1; -6,0 kkal/mol serta memiliki interaksi spesifik berupa ikatan hidrogen terhadap residu asam amino Arg109, Thr101 dan Lys102 pada situs aktif reseptor.

Synthesis, activity test and molecular docking of nitrophenylcalix[4]-2-methylresorcinarene derivatives as antimalarial and antioxidant agents have been carried out. Calix[4]-2-methylresorcinarene derivatives were synthesized in one step reaction through cyclocondensation reaction by reacting resorcinol and aldehydes, i.e., 2-nitrobenzaldehyde, 3-nitrobenzaldehyde and 4-nitrobenzaldehyde. The reaction was carried out through the reflux method with ethanol and hydrochloric acid 37% as the solvent and catalyst, respectively. The synthetic products were characterized using FTIR, 1H-NMR, 13C-NMR, and LC-MS spectrometers. The antioxidant test was conducted using DPPH (2,2-diphenyl-1-picrylhydrazyl) method while the antimalarial activity test was carried out in vitro against Plasmodium falciparum 3D7. The results showed that the C-2-nitrophenylcalix[4]-2-methylresorcinarene (2NK), C-3-nitrophenylcalix[4]-2-methylresorcinarene (3NK) and C-4-nitrophenylcalix[4]-2-methylresorcinarene (4NK) compounds were successfully synthesized. Compounds 2NK, 3NK and 4NK had 86.4, 78.6 dan 95.7% yield, respectively. Compounds 2NK, 3NK and 4NK had antioxidant activity with IC50 values of 116.10, 135.85 and 93.76 µg/mL, therefore, 2NK and 3NK compounds were categorized as moderate while 4NK was categorized as a strong antioxidant compound. The antimalarial activity test of 2NK, 3NK and 4NK gave IC50 values of 2.35, 1.68 and 1.79 µM, therefore, these compounds are classified as active as antimalarial compounds. Molecular docking performed against the P. falciparum lactate dehydrogenase (PfLDH) receptor showed that the 2NK, 3NK and 4NK compounds had negative binding affinity values of -5.1; -6,1; 6,0 kcal/mol and had specific interactions in the form of hydrogen bonds to the amino acid residues Arg109, Thr101 and Lys102 in the active site of the receptor.

Kata Kunci : antimalaria, antioksidan, kaliks[4]resorsinarena, PfLDH, Plasmodium falciparum 3D7