ABSTRACT ANTIBACTERIAL ACTIVITY OF CHALCONE DERIVATIVES FROM MACARANGA TRICHOCARPA AND SYNTHETIC

• Main Author: SALMAN FAREZA, MUHAMAD
• Format: Dissertations
• Language: Indonesia
• Subjects: Kimia
• Online Access: https://digilib.itb.ac.id/gdl/view/23176
• Institution: Institut Teknologi Bandung

Diseases caused by microbial infection are still a global concern, especially to the people in the tropical countries. The concern is, in particularly, due to the development of microbial resistances against available antibiotics. Therefore, seraching new antimicrobial compounds is still a potential research area until now. Traditionally, secondary metabolites produced by microorganisms are the source of antimicrobial compounds, however plants and synthetic compound can be also become an alternative sources. Chalcone derivatives, which are metabolites from plants, are potential one’s candidate for antimicrobial agents, and include in this group are compounds that have flavanone, dihydrochalcone, and chalcone basic structure. Compounds such as floretin (dihydrochalcone), 4- hidroxyderisine (chalcone), and exiguaflavanone D (flavanones), have been reported as strong antibacterial agents. In this research, isolation and synthesis of a number of chalcone derivatives have been carried out, as well as their antibacterial properties agains eight pathogenic bacteria. Flavanones and dihydrocalcones were obtained from the leaf extract of an endemic plant from Kalimantan island, namely Macaranga trichocarpa (Euphorbiaceae), while the chalcones were prepared by a synthesis. The pathogenic bacteria include two Gram-(+) bacteria Bacillus subtilis and Staphylococcus aureus, and six Gram-(-) becteria, Enterobacter aerogenes, Escherichia coli, Pseudomonas aeruginosa, Shigella dysenteriae, Vibrio cholera, and Salmonella typhi was used in this research. Isolation of flavanones and dihydrochalcones was carried out according the method previously described, which are including extraction, fractination and purification. Synthesis of chalcone derivatives were carried out using Claisen- Schmidt and oleffin methatesis reaction. Structure of the molecules were determined based on spectroscopic data, including UV, IR, 1D NMR (1H and 13C) and 2D NMR (COSY, HSQC, and HMBC), and mass spectral data. Antibacterial determination was carried by a microdilution method, and the antibacterial potency was evaluated with a minimum inhibition concentration (MIC) and minimum bactericidal concentration (MBC) which presented in ?g/mL. This research was achieved 21 chalcone derivatives, namely macatrichocarpin A (1), macatrichocarpin B (2), macatrichocarpin C (3), macatrichocarpin D (4), oxymacatrichocarpin C (5), and isomacatrichocarpin C (6), 7-O-methylnaringenin (7) and 4',7-di-O-methylnaringenin (8), 2'-hydroxy-4,4'-dimethoxychalcone (9), 4- allyloxy-2'-hydroxy-4'-methoxychalcone (10), 4-allyloxy-2-hydroxy-4'- methoxychalcone (11), 4,4'-diallyloxy-2'-hydroxychalcone (12), 2',4',4- trimethoxychalcone (13), 4-allyloxy-2',4'-dimethoxychalcone (14), 4'-allyloxy-2',4-dimethoxychalcone (15), 4,4'-diallyloxy-2'-methoxychalcone (16), 2'- allyloxy-4,4'-dimethoxychalcone (17), 2',4-diallyloxy-4'-methoxychalcone (18),2',4'-diallyloxy-4-methoxychalcone (19), 2',4',4-triallyloxychalcone (20), and a chalcone-eugenol derivative (21). Compounds 1, 2, 7 and 8 have basic structures of a flavanone, compounds 3-6 have basic structures of a dihydrochalcone, while compounds 9-21 contain basic structures of a chalcone. Compounds 1-8 were obtained from the leaves of M. trichocarpa and compounds 9-21 were prepared from synthesis. Based on the literature, compounds 5, 6, 10, 14-18 and 21 were new compounds. Antibacterial evaluation was showed that the antibacterial properties of the chalcone derivatives 1-21 have variety antibacterial properties, from weak to strong, with MIC values in the range of MIC 9,4 to > 150 ?g/mL. Compounds with flavanone structures were found to be more active than the others derivatives. The presence of isoprenylated groups, particularly in the chalcone derivative structures, can increase their antibacterial properties. However, oxygenation of this group gave an opposite effect. Methylation on the –OH groups, that produces O-methylated compounds, has a role in the increasing antibacterial properties. Although not significant, the the compounds with chelated –OH group were also to have higher antibacterials activites. The effect of the presence of allyl groups at C-4’ almost no effects or even can decrease the antibacterial properties. But, the opposite effect of this group was shown if it is position at C-4. Compound 21, a chalcone-eugenol derivative, showed weakly antibacterial properties than the precursors (compound 10 and eugenol). In conclusion, this research was successed to isolate and synthesize nine new chalcone derivative compounds, together with twelve known compounds. The research has also revealed antibacterial properties of those compounds and their structure activity relationship. The results of this research can be a starting point to develope an antibacterial compounds from chalcone derivatives. <br />