Browsing by Author "Qaralleh, Haitham"

Antibacterial pharmaceutical research groups are paying more attention to find novel antibiotics that could potentially overcome the development of bacterial resistance for the conventional antibiotics. In this study, four sponge species and three hard coral species were collected and identified based on their morphology, skeleton, and spicules characteristics. The sponge species investigated were Neopetrosia exigua, Xestospongia testudinaria (Langkawi), Xestospongia testudinaria (South China Sea) and Xestospongia sp. while the hard coral species investigated were Favites sp., Galaxea fascicularis, and Galaxea astreata. The collected species were extracted with deionized water followed by dichloromethane and methanol. The extracts were screened using disc diffusion and microdilution methods for antimicrobial activity against six pathogenic microorganisms. The result showed that aqueous and organic extracts of N. exigua exhibited potent activity against Bacillus cereus (inhibition zone 25 mm and MIC value of 0.07 μg/mL), Staphylococcus aureus (17.5 mm and 0.12 μg/mL) and against Candida albicans (21 mm and 0.32 μg/mL). N. exigua biomass extract was then subjected to bioassay guided isolation using sequential gradient partitioning with normal and reverse phase chromatography. From the polar fractions, four potent compounds were isolated, for the first time from N. exigua, hyrtiosine (34 μg/mL), demethylcystalgerone (11 μg/mL), xestospongien (11 μg/mL) and bisulfate avarol derivative (RnD1c) which was reported as a new natural product with potent bacteriostatic (2.6 μg/mL) and bactericidal (5.2 μg/mL) activities against S. aureus. The mode of action of RnD1c against S. aureus was investigated using a combination approach. Scanning Electron Microscope showed that RnD1c caused severe cell surface alteration of S. aureus. As a result of treating S. aureus with RnD1c, autolytic enzymes were triggered, N-acetylglucosamin synthesis was inhibited, membrane permeability was increased, leakage of ions was induced, intracellular ATP was decreased, arginine dihydrolase was inhibited and membrane depolarization was induced. The results imply that RnD1c exhibited multiple antibacterial mechanisms including acting upon bacterial cell membrane and cell wall. In conclusion, the species of sponge and coral collected from Malaysia have been shown to possess antimicrobial activity. RnD1c exhibited multiple antibacterial mechanisms including acting upon bacterial cell membrane and cell wall. These abilities highlighted it as a good lead compound for developing new antibiotics. This study commenced on Nov, 2008 and completed on Jan, 2012.