PHENOLIC DERIVATIVES OF KAEMPFERIA PANDURATA AND PINOSTROBIN (5-HYDROXY-7-METHOXY- FLAVANONE) ANALOG COMPOUNDS AND THEIR ANTIBACTERIAL PROPERTIES

• Main Author: DEWI MARLIYANA ( NIM : 30511013 ), SOERYA
• Format: Dissertations
• Language: Indonesia
• Online Access: https://digilib.itb.ac.id/gdl/view/24342
• Institution: Institut Teknologi Bandung

Kaempferia pandurata (syn. Boesenbergia rotunda, B. pandurata (Roxb.) Schltr), locally known as "Temu Kunci"in Indonesia, is one of the medicinal plants of the family Zingiberaceae. This plant has been used to cure various diseases, including health problems related to microbial infection (diarrhea, indigestion, dental caries, fungal infections), inflammation (fever, arthritis and muscle pain), asthma, itching, colic disorder, and dry cough. Phytochemical studies on the rhizome of K. pandurata showed the presence of flavonoid derivatives, namely flavanones and chalcones, which constitute as the main components of this plant. Bioactivity studies on this species exhibited various biological activities, such as antibacteria, anti-inflammatory, antitumor, anti-diarrhea, antidisentri, anti-HIV, antioxidant, antipyretic, analgesic and insecticides. Among the biological activities, the antibacterial activity results are important as an attempt to answer the emergence of resistance of some bacteria against existing drugs, as well as the emergence of a number of outbreaks of disease caused by bacteria. Therefore, a search to find new compounds that are potential as an antibacterial is an urgent matter. Compounds with antibacterial activities can be obtained by an isolation from natural resources or from a transformation of natural compounds to obtain a new type of high molecular diversity. In this study, both approaches have been used to find new bioactive compounds with antibacterial properties from K. pandurata and a transformation products of its major component. Isolation of the phenolic compounds of the K. pandurata rhizome, collected from Surakarta, Central Java, was carried out through extraction (maceration), fractionation, and purification. Fractionation and purification were done using various chromatographic techniques. Four compound were isolated and were identified based on NMR spectral data (1H and 13CNMR, COSY, HSQC, HMBC, and NOESY) as pinostrobin (1), pinocembrin (2), panduratin A (3), and 4- hidroxypanduratin A (4). Compound 1 was a major component of the rhizome and was further chemically transformed. Chemical transformation of compound 1 included prenylation and cyclization reactions to give nine transformation compounds. These compounds included monooxyprenyl pinostrobin (5), monooxyprenyl chalcone (6), diprenyl chalcone (7), tryprenyl chalcone (8), tryprenyl cyclohexene chalcone (9), monosyclicprenyl chalcone (10), monosyclicprenyl pinostrobin (11), monoprenyl chalcone (12), and monoprenyl pinostrobin (13). The formation of compounds 6, 7 and 8 were thought to proceed via prenylation of pinostrobin (1) followed by a perycyclic reaction and Claisen rearrangement, whereas compound 9 was formed through similar Claisen rearrangement but with a dearomatization reaction. A literature search showed that compounds 6-12 are new compounds. Antibacterial activities of compounds 1-13 were performed against nine ATCC bacteria (Bacillus cereus ATCC 21772, Bacillus subtilis ATCC 6633, Staphylococcus aureus ATCC 29737, Listeria monocytogenes ATCC 1531, Proteous mirabilis ATCC 21100, Vibrio parahaemolyticus ATCC 17802, Samonella typhi ATCC 14028 , Klebsiella pneumoniae ATCC 13733, Escherichia coli O157: H7), and eight bacteria of clinical isolates (Staphylococcus aureus, Bacillus subtilis, Escherichia coli, Salmonella typhi, Shigella dysenteriae, Enterobacter aerogenes, Pseudomonas aeruginosa, Vibrio cholerae). For the natural compounds, the results showed that panduratin A (3) and 4- hydroxypanduratin A (4) exhibited high activities against almost all ATCC bacteria, with MIC values in the range of 0.9 to 9.4 µg/mL. The two compounds also showed strong activities against S. aureus and B. subtilis of clinical isolates, with MIC values were 2.4 to 18.8 µg/mL. From these results, panduratin A (3) and 4-hydroxypanduratin A (4) are potential as a new antibacterial compounds. For the compounds of transformation products, only the monoprenyl chalcone 12 that has significant activities against S. aureus, P. mirabilis and K. pneumonia, with MIC values in the range of 7.8 to 62.5 µg/mL. The other compounds, namely compounds 5-11 and 13, showed only weak activities. These results indicated that chemical transformation of pinostrobin (1) to its derivatives, such as compound 12, can be an alternative source for new antibacterial compounds. Based on these MIC values it is suggested that a changing substituent at C-4 from a methoxyl group in panduratin A (3) to the hydroxy group in 4- hydroxypanduratin A (4) does not alter significantly their antibaterial activities against ATCC bacteria. However, the presence of the methoxyl group in panduratin A (3) can increase its antibacterial activities against bacteria of clinical isolates of S. aureus and B. subtilis as compared with 4-hydroxypanduratin A (4). In addition, increasing hydrophobicity in compound 12, as compared with pinostrobin (1), could be a significant factor in enhancing its antibaterial properties. Time-kill test was performed to 4-hydroxypanduratin A (4) against four ATCC bacteria (P. mirabilis, S. aureus, B. cereus and B. subtilis). The results indicated that S. aureus and B. subtilis were completely killed within 2 hours at 1xMIC, 4 hours against B. cereus at 1xMIC, while P. mirabilis was killed within 30 minutes. at 2xMIC. These results can be used to determine the dose of 4- hydroxypanduratin A (4) for further clinical tests. <br />