Sintesis dan uji aktivitas Diasetil Pentagamavunon-1

JULIANUS, Jeffry, Dr. Supardjan AM., MS.,Apt

2006 | Tesis | S2 Ilmu Farmasi

Diasetil pentagamavunon-1 (diasetil PGV-1) atau 2,5-bis (4’asetoksi-3’,5’ dimetilbenzilidin) siklopentanon merupakan bentuk ester asetat dari pentagamavunon-1 (PGV-1) atau 2,5-bis (4’ hidroksi-3’,5’ dimetil benzilidin) siklopentanon. Asetilasi dilakukan untuk meningkatkan lipofilisitas dan bioavaibilitas PGV-1. Sintesis diasetil PGV-1 dilakukan dengan mereaksikan PGV-1 dan anhidrida asam asetat dalam suasana basa larutan natrium hidroksida 10% dalam etanol. Sintesis dilakukan dengan memvariasi perbandingan mol PGV-1 dan mol anhidrida asam asetat. Uji sitotoksik diasetil PGV-1 terhadap sel T47D dan sel raji dilakukan dengan metode metil tiazol tetrazolium (MTT) . Uji antioksidan diasetil PGV-1 dilakukan dengan menggunakan radikal bebas 2,2-difenil-1-pikril hidrazil (DPPH). Uji penghambatan ekspresi siklooksigenase (COX-2) diasetil PGV-1 dilakukan dengan menggunakan sel raji. Sintesis diasetil PGV-1 menghasilkan crude product sebesar : 0,815 g; 0,9342 g; 0,9602 g. Crude product dicuci dan direkristalisasi dengan etanol. Berdasarkan elusidasi struktur dengan infra merah, spektrofotometri UV-Vis, Resonansi magnetik inti (1H-NMR), dan spektroskopi massa, disimpulkan bahwa senyawa hasil sintesis adalah diasetil PGV-1 dan diketahui pengotornya adalah monoasetil PGV-1. Senyawa hasil sintesis mempunyai jarak lebur 240,1°C- 241,4°C dan dari hasil kromatografi cair kinerja tinggi menunjukkan senyawa hasil sintesis mempunyai kemurnian 92,43 %. Hasil uji sitotoksik menunjukkan diasetil PGV-1 mempunyai efek sitotoksik terhadap sel T47D dan sel raji yang lebih rendah dibanding PGV-1. Pada konsentrasi 40 μM, yang merupakan konsentrasi tertinggi diasetil PGV-1 mengakibatkan kematian sel raji sebesar 33,52 %. Hasil uji antioksidan menunjukkan diasetil PGV-1 mempunyai aktivitas antioksidan yang lebih rendah dibanding PGV-1. Hasil uji menunjukkan diasetil PGV-1 lebih menghambat ekspresi COX-2 dibanding PGV-1.

Diacetyl pentagamavunon-1 or 2,5-bis (4’ acetoksi-3’,5’ dimethylbenzylidene) cyclopentanon is an acetic ester of pentagamavunon-1 or 2,5-bis (4’ hydroxyl-3’,5’ dimethylbenzylidene) cyclopentanon. Acetylation has been done in order to improve lipofilicity of PGV-1 and increases it’s bioavaibility. Synthesis of diacetyl PGV-1 was done by reacting PGV-1 and acetic acid anhydride in base condition of sodium hydroxide 10% in ethanol. Synthesis was carried out in variety of equivalent mol PGV-1 and mol acetic acid anhydride. Cytotoxicity test of diacetyl PGV-1 to T47D cells and raji cells was carried out by methyl thiazol tetrazolium method (MTT). Antioxidant test of diacetyl PGV-1 was carried out using free radical 2,2-diphenyl-1-picryl hidrazyl (DPPH). The test of inhibition cyclooxygenase-2 (COX-2) expression of diacetyl PGV-1 was carried out using raji cells. Synthesis of diacetyl PGV-1 yield crude product of 0,8512 g; 0,9342 g; 0,9602 g respectively. The crude products were washed with ethanol and recristalized from ethanol. Based on structure elucidation with infra red, UV-Vis spectrophotometric, nuclear magnetic resonance (1H-NMR), and mass spectroscopy, it can be conclude that synthetical compound is diacetyl PGV-1 and it’s impurities is monoacetyl PGV-1. Synthetical compound has melting point range between 240,1oC-241,4oC and from high performance liquid chromatography synthetical compound has 92,43 % of purity. The result of cytotoxicity test showed cytotoxic effect of diacetyl PGV-1 to T47D cells and raji cells was weaker than PGV-1. At concentration 40 μM which was the highest concentration of diacetyl PGV-1 caused 33,52 % death of raji cells. The result of antioxidant test showed antioxidant effect of diacetyl PGV-1 was weaker than PGV-1. The result showed diacetyl PGV-1 more inibit COX-2 exprresion than PGV-1.

Kata Kunci : Diasetil PGV,1,Sel T47D dan Sel Raji, diacetyl PGV-1, T47D cells, raji cells, cytotoxicity, antioxidant, COX-2