Studies on the Novel Bioactive Terpenoids and Saponins from a Tropical Marine Sponge, Lipastrotethya sp.
열대 해면 Lipastrotethya sp. 유래의 생리활성 terpenoids 와 saponins 에 대한 연구
- 약학대학 약학과
- Issue Date
- 서울대학교 대학원
- 학위논문 (박사)-- 서울대학교 대학원 : 약학과 천연물과학전공, 2015. 8. 신종헌.
- Researches on marine natural products have been grown rapidly from the late 1960s upward with developments of methods of isolation, analysis, and structure determination. After marine natural products are proven as potent sources therapeutic agents that may be directly used as drugs or served as lead structures for drug development due to their high novelty of bioactivities and chemical structures, there were enormous efforts to investigate new drugs and achievements
Since the 1960s, more than 20,000 compounds were discovered from marine organisms and over 1000 compounds are reported annually after 2008. Majority of novel compounds, approximately 75%, were isolated from marine invertebrates belonging to the phyla Porifera and Coelenterate. Due to its wide distribution, the diversity in species, convenience of collection, and a wide range of chemical class for metabolites, sponges takes important place in marine natural products and are very highly regarded as subject of study.
This study is searching novel bioactive marine natural products from a torpical marine sponge, Lipastrotethya sp. which was collected in Micronesia. The research aimed to improve the availability of marine natural products in the industry and essentioal technologies needed to develop lead compounds for natural product-based drug discovery. By the chemical methods, spectroscopic analysis, and bioactivity tests, the sponge, Lipastrotethya sp., was selected and pure 25 compounds were isolated from the extract by various chromatographic methods. Finally, 14 novel compounds and 11 known compounds are determined using combined spectroscopic and chemical analyses. There were 7 compounds of pouoside-class, 5 compounds of corresponsive sapogenins, and 13 compounds of sarasinoside-class. All isolates have been examined under various bioactivity: cytotoxicity test (K562 human erythroleukemia cell, A549 lung carcinoma cell), antimicrobial activity test (gram-positive bacteria, gram-negative bacteria, and pathogenic fungi), enzyme-inhibitory activity test (Na+/K+ ATPase, Isocitrate lyase, Sortase A). Several compounds displayed significant cytotoxic, and/or enzyme-inhibitory activities.
1. Triterpene Galactosides of the Pouoside Class and Corresponding Aglycones from the Sponge Lipastrotethya sp.
Nine new triterpene galactosides and aglycones, along with three known compounds from the rare pouoside class, were isolated from the tropical sponge Lipastrotethya sp. collected from Micronesia. The structures of these new compounds were determined by combined spectroscopic methods and designated as pouosides F-I (4, 8, 10, and 12) and pouogenins A-E (5?7, 9, and 11). The absolute configurations of the asymmetric centers and the cyclohexenone moiety, which had been previously undetermined, were assigned by NOESY analyses and Moshers methods. Several of these compounds exhibited weak cytotoxicity against the K562 cell-line.
2. Nortriterpene Glycosides of the Sarasinoside Class from the Sponge Lipastrotethya sp.
Five new nortriterpene glycosides, along with eight known compounds of the sarasinoside class, were isolated from the tropical sponge Lipastrotethya sp. collected from Chuuk, Micronesia. The structures of these new compounds were determined by combined spectroscopic and chemical methods and designated as sarasinosides N?R (21?25). The aglycone portions of 22?25 were found to be unprecedented among nortriterpeneoids on the basis of extensive NMR analyses. Several of these compounds exhibited cytotoxicity against A549 and K562 cell lines as well as weak inhibitory activity against Na+/K+-ATPase.