SECONDARY METABOLITES FROM STEM BARK OF GARUGA FLORIBUNDA, CHEMICAL TRANSFORMATION OF BIPHENYL DIARYLHEPTANOID ALONG WITH THEIR BIOACTIVITY TEST

• Main Author: Shofihatul Qolby, Denisa
• Format: Theses
• Language: Indonesia
• Subjects: Kimia
• Online Access: https://digilib.itb.ac.id/gdl/view/56023
• Institution: Institut Teknologi Bandung

Natural products have an important role in drug discovery and development. Most of drugs made from natural products were obtained from plants. One of plants known to have pharmacological properties is Garuga genus. This genus is known to produce cyclic diarylheptanoids as its major secondary metabolites. Cyclic diarylheptanoids is reported to have various bioactivities, such as anticancer, antibacterial, antioxidant, antidiabetic, and antiinflammatory. One of Garuga species growing in Indonesia is Garuga floribunda. Previous investigation reported that stem bark of Indonesian G. floribunda yielded three diphenyl ether type cyclic diarylheptanoids (garuganin I, garugamblin I, 9’-desmethylgarugamblin I) and one new biphenyl type cyclic diarylheptanoid, i.e. Gf-3. Their bioactivity as an anticancer is potential to be studied in this research. It is also known that cyclic diarylheptanoid from Garuga has similar structure to rifamycin SV having good activity as an antibacterial, hence it also opens the opportunity of compounds from Garuga to be studied for their antibacterial activity. Therefore, in this research continuing isolation of other compounds from stem bark of G. floribunda Indonesia has been conducted as well as chemical transformation of a major compound and their cytotoxicity test against murine leukemia P-388 cells. The research began with the isolation of secondary metabolites from G. floribunda stem bark by extraction in room temperature (maceration), fractionation and purification by using several chromatography methods, such as Vacuum Liquid Chromatography (VLC), Radial Chromatography (RC) and Gravitational Column Chromatography (GCC). In chemical transformation process of a cyclic diarylheptanoid, protection of free phenolic group using prenyl and allyl groups has also been carried out. In this research, eleven compounds have been obtained, nine of them were cyclic diarylheptanoids. Four of nine compounds have been reported previously, but they were yielded in this continuing research. The compounds included three diphenyl ether type cyclic diarylheptanoids (garuganin I, garugamblin I, 9’- desmethylgarugamblin I) and one biphenyl type (Gf-3). Meanwhile, five other cyclic diarylheptanoids were recently reported in this research, three of them were suggested as new compounds consisting one biphenyl type (Gf-6) and two diphenyl ether type (Gf-9, Gf-10). Two other compounds were known biphenyl type, namely garuganin V and garuganin II. In addition, two other compounds were a steroid derivative (?-sitosterol) and a triterpenoid (3?-hydroxytirucalla-7,24-dien-23- one). Moreover, two chemical transformations (prenylation and allylation reactions) on garuganin V as major compound of G. floribunda stem bark have also been conducted. In a prenylation reaction, one compound was produced, namely PR-1 (33.1%). Besides that, an allylation yielded AL-1 (32,8%). The cytotoxic examination on four cyclic diarylheptanoids against murine leukemia P-388 cells showed that 9'-desmetylgarugamblin I and Gf-3 were very active and active (IC50 < 0.1 and 2.23 ?g/mL), meanwhile garuganin I and garugamblin I was inactive (IC50 > 4.0 ?g/mL).