SINTESIS ORGANIK GELOMBANG MIKRO SENYAWA 1,5-Bis(3-Etoksi-4-Hidroksifenil)-1,4-Pentadien-3-on (EHP) DAN UJI IN SILICO INHIBISI COX-2 SERTA UJI AKTIVITAS FARMAKOLOGI

ESTI MUMPUNI, Prof. Dr. Umar Anggara Jenie, M.Sc., Apt; Prof. Dr. Harno Dwi Pranowo, M.Si.; Dr. Arief Nurrochmad,M.Si., M.Sc., Apt.

2016 | Disertasi | S3 Ilmu Farmasi

Senyawa 1,5-bis(3-etoksi-4-hidroksifenil)-1,4-pentadien-3-on (EHP) adalah analog kurkumin. Metode sintesis awal senyawa ini mengacu pada metode tanpa pelarut dengan mekanisme reaksi kondensasi aldol, yang rendemen hasil sintesis kurang memuaskan dan membutuhkan waktu yang relatif lama. Pada penelitian ini dilakukan sintesis senyawa EHP dengan bantuan paparan gelombang mikro, karakterisasi dan elusidasi senyawa tersebut dengan berbagai jenis instrumen, uji in silico inhibisi COX-2, uji sitotoksik terhadap sel WiDR dan ekspresi COX-2, daya antiinflamasi serta uji antimikroba. Sintesis dengan bantuan gelombang mikro (Microwave-Assisted Organic Synthesis/MAOS) dianggap sebagai green technology terutama karena dengan metode ini dapat dilakukan reaksi organik dengan kondisi sehemat mungkin bahan kimia (efisiensi atom), penggunaan energi dan efisiensi waktu reaksi. Hasil penelitian menunjukkan bahwa senyawa EHP dapat disintesis dengan bantuan gelombang mikro menggunakan perbandingan mol etil vanillin : aseton (2:1), pelarut metanol dan katalis asam klorida menghasilkan rendemen mencapai lebih 90% dengan nilai efisiensi atom dan limbah sesuai prinsip green chemistry. Hasil uji in silico senyawa EHP tidak menginhibisi COX-2, uji sitototoksik senyawa EHP pada sel kanker kolon WiDR mempunyai nilai IC50 90 ppm dan mengekspresikan COX-2 sekitar 3%. Daya antiinflamasi EHP sekitar 74% dengan dosis 137,35 mg/200 g BB tikus per oral. Kadar Hambat Minimum senyawa terhadap mikroba Staphylococcus aureus (ATCC 25923), Escherichia coli (ATCC 25922), Salmonella typhi (ATCC 14028) 0,063 ppm.

1,5-bis (3'-ethoxy-4'-hydroxyphenyl)-1,4-pentadien-3-one (EHP) is an analog of curcumin. Previously the compound has been already synthesized without the addition of solvent, however the results was unsatisfied. This physicochemical characterization, and its activity of this EHP compound have not been done yet. In this research, we succesfully modified and synthesized the compound with microwave exposure. Physicochemical properties were characterized, cytotoxicity and COX-2 expression were studied using WiDR cells, antiinflammatory and antimicrobial activity were also performed. In silico test was done to know the COX-2 inhibition. Microwave-assisted synthesis (Microwave-Assisted Organic Synthesis / MAOS) were considered as a green technology method because the organic reaction could be done with less chemical materials (atom efficiency), less energy, and less time reaction. The results showed EHP could be synthesized by microwaves help with mole ratio of ethyl vanillin: acetone (2: 1). Methanol was used as solvent and hydrochloric acid was used as catalysts. The yield reached over 90% with atom efficiency and minimal waste corresponding to green chemistry.The in silico test results that EHP could not inhibit COX-2. The cytotoxic test against WiDR cell had IC50 value of 90 ppm and expressed COX-2 about 3%. EHP had antiinflammatory power about 74% at a dose of 137.35 mg/200 g BW rats orally. The EHP Level of Minimum Inhibitory against microbes Staphylococcus aureus (ATCC 25923), Escherichia coli (ATCC 25922), Salmonella typhi (ATCC 14 028) were 0.063 ppm.

Kata Kunci : sintesis EHP, gelombang mikro, in silico, aktivitas farmakologi