Sintesis dan uji aktivitas antioksidan senyawa tetrahidropentagamavunon (THPGV-0)

SIMBARA, Ari, Dr. Sardjiman, M.S., Apt

2009 | Tesis | S2 Ilmu Farmasi

Kurkumin 1, tetrahidrokurkumin 3, dan turunan kurkumin struktur monoketon, pentagamavunon-0 (PGV-0) 9 telah banyak diteliti dan terbukti mempunyai aktivitas antioksidan, antiinflamasi dan antikanker. Namun, dalam studi farmakokinetik, kurkumin 1 dan PGV-0 9 menunjukkan bioavailabilitas sistemik yang rendah setelah pemberian dosis oral dalam studi preklinik. Upaya pengembangan obat baru selanjutnya adalah sintesis senyawa tetrahidropentagamavunon-0 (THPGV-0) 10 yang diperkirakan sebagai metabolit aktif dari PGV-0 9. Metode sintesis THPGV-0 10 adalah dengan cara hidrogenasi PGV-0 9 menggunakan katalis Pd/C 10% dan gas hidrogen pada suhu kamar. Hasil sintesis dianalisis berdasarkan titik lebur, kromatogram KLT dan GC, dan elusidasi struktur menggunakan metode spektrometri UV, IR, Massa, 1H-NMR, dan 13C-NMR. Uji daya antioksidan menggunakan metode DPPH Radical Scavenging dan Ferric Reducing Antioxidant Power (FRAP). Hasil penelitian diperoleh senyawa THPGV-0 10 yang berbentuk serbuk putih dengan jarak lebur 122,2-123,4 oC. Rendemen hasil sintesis adalah 24,52 %. Berdasarkan uji aktivitas antioksidan, THPGV-0 10 mempunyai daya tangkap terhadap radikal DPPH 40 lebih baik dibandingkan dengan PGV-0 9 dan vitamin E 44 dengan nilai ES50 THPGV-0 10, PGV-0 9, dan vitamin E 44 berturutturut 29,19; 64,56; 47,87 mM. Selanjutnya, berdasarkan nilai Ferric Reducing Antioxidant Power (FRAP), THPGV-0 10 mempunyai nilai FRAP lebih besar daripada PGV-0 9 dan vitamin E 44. Ini menunjukkan bahwa THPGV-0 10 mempunyai potensi yang besar sebagai senyawa antioksidan sehingga perlu diteliti lebih lanjut untuk aktivitas biologis yang lain seperti antikanker, antidiabetes, dan antiinflamasi.

Curcumin 1, tetrahydrocurcumin 3, and monoketone curcumin analogue, pentagamavunone-0 (PGV-0) 9 have been investigated as antioxidant, antiinflammatory, and anticancer. But, based on pharmacokinetic studies, curcumin 1 and PGV-0 9 have demonstrated low systemic bioavailability following oral dosing in preclinical animal studies. The next study of this compound s is synthesis of tetrahydropentagamavunone-0 (THPGV-0) 10 compound. This compound is assumed as active metabolite from PGV-0 9. Synthesis of THPGV-0 10 through hydrogenation method of PGV-0 9 using Pd/C 10% as catalyst and hydrogen gas at room temperature. The result of synthesis was analysed based on melting point, TLC and GC chromatogram data, and structure elucidation by UV, IR, Mass, 1H-NMR, and 13C-NMR spectrometric. Then, the compound was tested for antioxidant activities by DPPH Radical Scavenging and Ferric Reducing Antioxidant Power methods. The synthesis result, THPGV-0 was as white powder with melting point 122,2-123,4 oC. Rendement: 24,52 %. Based on antioxidant tests, THPGV-0 10 was more effective DPPH-radical scavenging than PGV-0 9 and vitamin E 44 with level of ES50 THPGV-0 10, PGV-0 9, and vitamin E 44 were 29,19; 64,56; 47,87 mM; respectively. The level of Ferric Reducing Antioxidant Power (FRAP) of THPGV-0 10 was higher than PGV-0 9 and vitamin E 44. Generally, THPGV-0 10 have high potency as antioxidant compound so need development reseach for other biologic activities such as anticancer, antidiabetic, and anti-inflammatory.

Kata Kunci : THPGV,0,Synthesis,Antioxidant