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Chemical Constituents Of Two Solanum Species, Microbial Transformation And Biological Activities

Posted on:2011-06-30Degree:DoctorType:Dissertation
Country:ChinaCandidate:Y ZhaoFull Text:PDF
GTID:1114360305950937Subject:Medicinal chemistry
Abstract/Summary:PDF Full Text Request
The genus Solanum, which belongs to family of Solanaceae, is a very large group. About 2000 species are found throughout the temperate and tropical regions of the world. There are 39 species in China, and about 20 species of them have been used as traditional Chinese medicine to treat cancer, gonorrhea, ulcers, wounds, burns and so on. Various types of steroidal glycoalkaloids and steroidal saponins, which showed significant biological activities, were isolated from the genus in the past decades. Now the genus Solanum have been well know as a source of biologically active and naturally occurred compounds. Steroid compounds can be ranked among the most widely marketed products in the pharmaceutical industry. The production of steroid drugs and hormones is one of the best examples of the successful application of microbial technology in large scale industrial processes. Conversions of steroids by microorganisms are commonly achieved in mild conditions and are efficient tools to introduce functional groups into chemically inaccessible sites of steroid molecules.25 compounds were obtained from the aerial parts of S. nigrum L., compounds 8,9,16-18,23 are isolated from this species for the first time. Solamargine (4) exhibited strong cytotoxicity against K562, KB, K562/A02 and KB/VCR cells with IC50 values of 8.0,7.8,5.4 and 7.1μM. Solasodine (1) showed inhibitory effects in vitro against the plant pathogenic fungus Botrytis cinerea and Fusarium oxysporum f. sp. lycopersici. Almost complete inhibition of mycelial growth was observed at the concentrations of 8 and 2μg/ml. After a week of inoculated with the spore suspension of F. oxysporum, plants were sick, and compounds 1-5 were all accumulated in the roots and aerial parts. This may reveal the ecological role of the steroidal alkaloids.25 compounds were isolated from the aerial parts of S. melongena L., and 24 compounds were identified. Compounds 37 and 42 are isolated from this species for the first time, which shed lights on chemotaxonomy and chemical ecology of this plant species.Microbial transformation of diosgenin (6) by Syncephalastrum racemosum and Absidia coerulea yielded 10 new distinct polar metabolites. The 9α- and 12/β-hydroxylation are difficult to achieve by chemical means and has potential to produce useful compounds, which were starting materials for the production of 9a-halogen corticoids and 12β-hydroxy-androstenes. Effects of biotransformation time, initial pH and the concentration of 6 on transformation rate by S. racemosum have been investigated. The products 47-56 were tested for antiproliferative activity against K562 and KB cell lines in vitro. Compounds 47 and 51 were found to be more potent than the parent compound 6 against K562 with IC50 values of 26.5 and 21.4μM, while compounds 48 and 51 were found to be more potent than the parent compound against KB with IC50 values of 19.7 and 22.1μM.γ-solamargine (2) interfered with the biofilm formation of Candida albicans through downregulating the expression of adhesion and hyphae specific genes, and inhibiting the adhesion stage and the formation of hyphae. Compound 2 were found to be more potent against the formation of hyphae in the culture media which did not contain glucose.
Keywords/Search Tags:Solanum, Steroidal glycoalkaloids, Steroidal saponins, Solamargine, Antifungal activity, Antiproliferative activity, Microbial transformation, Biofilms
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