STUDI PENAMBATAN MOLEKUL, SINTESIS, DAN UJI BIOAKTIVITAS ANTIPLASMODIUM SENYAWA POLISIKLIK γ-LAKTAM

M. ROSYID H, Dr. M. Idham Darussalam M., S.Sc.; Prof. Dr. Chairil Anwar

2023 | Skripsi | S1 KIMIA

Telah dilakukan studi tentang potensi senyawa polisiklik γ-laktam sebagai kandidat antiplasmodium. Penelitian diawali dengan penambatan molekul tiga senyawa polisiklik γ-laktam A, B, dan C terhadap protein Plasmodium falciparum dihydrofolate reductase enzyme (PfDHFR), Plasmodium falciparum Enoyl-Acyl-Carrier Reduktase Gene (PfENR), dan Plasmodium falciparum Heat shock protein 90 (PfHsp90). Penambatan molekul dilakukan menggunakan software AutoDockTools untuk mengetahui nilai energi ikatan dan interaksi yang terbentuk antara senyawa turunan polisiklik γ-laktam dengan sisi aktif protein. Selanjutnya, senyawa polisiklik γ-laktam disintesis dengan bahan dasar anhidrida ftalat dan aminopropanol melalui reaksi kondensasi, reduksi, dan siklisasi intramolekul. Produk reaksi dielusidasi dengan spektrometer 1H-NMR, 13C-NMR, GC-MS, dan FTIR. Senyawa polisiklik γ-laktam hasil sintesis diujibioaktivitasnya sebagai senyawa antiplasmodium secara in vitro terhadap Plasmodium falciparum galur 3D7. Nilai energi ikatan hasil penambatan molekul senyawa polisiklik γ-laktam A, B, dan C terhadap protein PfDHFR adalah sebesar -4,24; -6,07; dan -5,71 kkal/mol, terhadap protein PfENR adalah sebesar -5,51; -7,47; dan -5,99 kkal/mol dan terhadap protein PfHsp90 adalah sebesar -4,68; -6,33; dan -5,26 kkal/mol.Berdasarkan hasil penambatan molekul polisiklik γ-laktam B dilanjutkan untuk disintesis dan diuji bioaktivitas antiplasmodium. Senyawa polisiklik γ-laktam B berhasil disintesis dengan tiga tahap reaksi dan diperoleh persen hasil berturut-turut adalah 97, 80, dan 86%. Hasil uji bioaktivitas antiplasmodium secara in vitro menunjukan senyawa polisiklik γ-laktam B memiliki nilai IC50 sebesar 97,726 µg/mL dan dikategorikan bioaktivitas kurang aktif terhadap Plasmodium falciparum galur 3D7.

Studies on potential of polycyclic γ-lactam compounds as antiplasmodial candidates have been conducted. The investigation began with the calculation of binding energy of three polycyclic γ-lactam compounds of A, B, and C towards Plasmodium falciparum dihydrofolate reductase enzyme (PfDHFR), Plasmodium falciparum Enoyl-Acyl Carrier Reductase Gene (PfENR) proteins, and Plasmodium falciparum Heat shock protein 90 (PfHsp90). The molecular docking study was carried out using AutoDockTools software to determine the binding energy and interactions formed between polycyclic γ-lactam derivative and the protein active site. Furthermore, polycyclic γ-lactam compounds were synthesized from the precursors of phthalic anhydride and aminopropanol through condensation, reduction, and intramolecular cyclization reactions. The reaction products were elucidated with 1H-NMR, 13C-NMR, GC-MS, and FTIR spectrometers. The synthesized polycyclic γ-lactam was subjected to antiplasmodium assay against Plasmodium falciparum strain 3D7 by in vitro. The binding energy of the molecular docking of polycyclic γ-lactam compounds A, B, and C to PfDHFR protein are -4.24; -6.07; and -5.71 kcal/mol, the PfENR protein are -5.51; -7.47; and -5.99 kcal/mol and for PfHsp90 protein, are -4.68; -6.33; and -5.26 kcal/mol. Based on the moleclar doking study, polycilclic γ-lactam B was synthesiszed and tested for be synthesized and tested for antiplasmodial activity. The polycyclic γ-lactam B was successfully synthesized in three reaction steps and the yield percentages of 97, 80, and 86%, respectively. The antiplasmodial activity assay by in vitro showed that the polycyclic γ-lactam B compound had an IC50 value of 97.726 g/mL and was categorized as less active against Plasmodium falciparum strain 3D7.

Kata Kunci : Penambatan molekul, Plasmodium falciparum galur 3D7, Polisiklik Laktam, Uji Plasmodium