Studies On The Two Chemical Constituents And Their Bioactives Of Two Species Of Higher Fungi

Fungi are widely distributed huge group of organisms. A large number of chemical constituents with novel skeleton were found in fungi, some of which possessing significant bioactivities have been developed to drugs or lead compounds. Recent years, higher fungi have been attractting more and more chemical and biological researchers.The chemical constituents and bioactivities of two species of higher fungi were studied. Fifty-three secondary metabolites were isolated from the fruiting bodies by silica gel, reversed-phase (RP), and Sephadex LH-20 column chromatographyies. Fourty-one compounds were elucidated by means of spectroscopic techniques, including 1D and 2D-NMR (1H-NMR, 13C-NMR, 1H-1HCOSY, HMQC, HMBC and NOESY) as well as mass spectrometry (ESI-MS, EI-MS, FAB-MS and HR-ESI-MS). Among isolated compounds, eight new isolated compounds were named as scabronine K, scabronine L, secoscabronine A, secoscabronine B, scabronine M, scabronine N, fasciculol H and fasciculol I, respectively; besides, Sarcodonin G and Sarcodonin A, showed significant neurite outgrowth (neuritegenesis)-promoting activity were also obtained. The results are concluded as follows:1. The edible mushroom Sarcodon scabrosus belongs to the family Polyporales. Thirty-two metabolites were isolated from the EtOAc extract and twenty-five of them were elucidated as scabronine K (1-1), scabronine L (1-2), secoscabronine A (1-3), secoscabronine A (1-4), scabronine M (1-5), scabronine N (1-6), sarcodonin G (1-7), sarcodonin A (1-8), Sarcodonin M (1-9), scabronine G (1-10), scabronine H (1-11), sarcodonin I (1-12), ergosta-7,22-dien-3β,5α,9α-trihydroxy-6-one (1-13), 3β,5α,9α-trihydroxy-6β-methoxyergosta- 7,22-dien (1-14), 3-O-β-D-Glucopyranosyl-5α,8α-epidioxyergosta-6,22-diene (1-15), cerevisterol (1-16), tuberoside (1-17) (2S,3R,4E,8E)-1-(β-D-glucopyranosyl)-3-hydroxy-2- [(R)-2′-hydroxyheptadecanoyl]amino-9-methyl-4,8-octadecadiene (1-18), ergosterol peroxide (1-19), Cholest-7en-3β-ol (1-20), ergosta-7,22-dien-3β-ol (1-21), ergosterol (1-22), 3β-hydroxy-24-methylcholesta-5,22-dien-7-one (1-23), benzoicacid (1-24), methyl p-hydroxybenzoate (1-25). scabronine K (1-1), scabronine L (1-2), secoscabronine A (1-3), secoscabronine B (1-4), scabronine M (1-5) and scabronine N (1-6) are new compounds.Among these compounds, only sarcodonins A and G (1-8 and 1-7) at 25μM showed significant neurite outgrowth (neuritegenesis)-promoting activityin the presence of 20 ng/mL NGF after 24 h treatment. Their structure-activity relationship was also discussed. 2. The toxic mushroom Naematoloma fasciculare belongs to the family Strophariaceae. Twenty-two metabolites were isolated from the EtOAc extract of the fruiting bodies of this fungus and sixteen compounds were elucidated as fasciculol H (2-1), fasciculol I (2-2), fasciculic acid C (2-3), ergosterol peroxide (2-4), 3-O-β-D-Glucopyranosyl-5α,8α- epidioxyergosta-6,22-diene (2-5), cholest-7-en-3β-ol (2-6), ergosta-7,22-dien-3β-ol (2-7), (2S, 3R,4E,8E)-1-(β-D-glucopyranosyl)-3-hydroxy-2-[(R)-2′-hydroxyheptadecanoyl]amino-9-methyl-4,8-octadecadiene (2-8), fasciculol B (2-9), fasciculol A (2-10), fasciculol C (2-11), cerevisterol (2-12), fasciculic acid F (2-13), fasciculol D (2-14), fasciculol G (2-15) and3β-hydroxy-24-methylcholesta-5,22-dien-7-one (2-16). fasciculols H (2-1) and L (2-2) are new compounds.The cytotoxic activities against Human malignant glioma cell line U87 of diosgenin, 2-1, 2-2, 2-3, 2-4, 2-5 and 2-6 were assessed by the XTT method. The five compounds showed certain cytotoxic activities which exhibited the inhibition rates of 13.12%,3.66 %,24.45 %,31.71 %,20.06 %,10.94 %, respectively, at a concentration of 100μM. The compounds 2-4 and 2-5 Showed relatively better activity than others.3. Sarcodonin G showed anti-tumor activity, it can inhibit the proliferation of HeLa cells with IC50 =7.19μM according to the literature. We prepared 25 derivatives using sarcodonins G (1-7) and A (1-8) as a substrate, of which 23 were new compounds. The cytotoxic activity of these derivatives were tested by brine shrimp lethal experiments but all the derivatives showed lower cytotoxicity than sarcodonins, and the lethality rate were less than 20% at the concentration of 100μM.In a conclusion, the chemical constituents and bioactivities of two higher fungi were studied in this thesis. The results provided the basis for discovery of bioactive lead compounds and provided theoretical foundation for further utilization of the mushroom Sarcodon scabrosus and Naematoloma fasciculare studied.