Bioactivity And Chemical Diversity From The Basidiomycete Cyathus Africanus And Streptomyces

In recent years,the secondary metabolites of microorganisms have aroused attentions of more and more chemical and biological researchers.A large number of chemical constituents with novel skeleton were found in microorganisms,some of which possessing significant bioactivities have been developed to drugs or lead compounds.The chemical constituents and their bioactivities of two Cyathus africanus,four Streptomyces and one Peltaster fructicola were studied.82 compounds were obtained from the cultures of the microbial materials.nineteen new compounds and one novel carbon skeleton cyathane diterpene were obtained.Compounds were isolated via various chromatographic methods(HPLC,MPLC,Sephadex LH-20 and normal silica and RP-silica column)and elucidated based on spectral data(1H-NMR、13C-NMR、HSQC、1H-1H COSY、HMBC、NOESY、HR-ESIMS、ECD).Most of the compounds were screened with bioactivity.The results are concluded as follows:1.Ten new cyathane diterpenes neocyathins A–J(1-10)were isolated from the fermentation broth of Cyathus africanus 5.1163.Compounds cyathin I(11),cyathin O(13),Allocyafrin B4(14)showed potent inhibition against iNOS in nerve cells with rates of45.88%,60.05%,55.38%,respectively.Compounds cyathin I(11),cyathin O(13)showed potent inhibition against COX-2 in nerve cells with rates of 53.9%,42.6%,respectively.The structure-activity relationship was discussed.Compounds were tested for their enhancement of NGF-induced neutrite outgrowth(neuritogenic activity)using rat pheochromocytoma(PC-12)cells as a model system of neuronal differentiation.Compounds neocyathin E(4),neocyathin E(5),neocyathin H(8),neocyathin I(9)showed increased neurite outgrowth activity.2.Seven new cyathane diterpenes named cyafricanin A–G(1-7),all these ten compounds were isolated from the fermentation broth of Cyathus africanus 5.1117.cyafricanin A presence of ring-opening between C-4 and C-9 from the cyathane carbon skeleton with an unprecedented 9/7 ring system.The biogenic pathway relationship have been discussed.Compounds were tested for their enhancement of NGF-induced neutriteoutgrowth(neuritogenic activity)using rat pheochromocytoma(PC-12)cells as a model system of neuronal differentiation.Cyafricanins A and B showed potent increased neurite outgrowth activity with rates of 35.1% and 31.7%,respectively.3.Two new polyoxygenated cyclohexenone,gabosines P(1)and Q(2),were isolated from the culture of the actinomycete Streptomycetes strain no.S8.These compounds were evaluated for α-glucosidase inhibitory activity in vitro.Only gabosine P(IC50 = 9.07 μM)exhibited higher potency than that of the control acarbose(IC50 = 663.281 μM).Molecular docking studies revealed the existence of hydrogen bonding and hydrophobic interaction between the enzyme and gabosine P.The structure-activity relationship was discussed.4.Twenty-four metabolites 1-24 were isolated from the fermentation broth of Streptomyces caa01.Compounds daidzein(1),genistein(2)and gliricidin(3)inhibitedα-glucosidase with IC50 values of 174.2,36.1,and 47.4 μM,respectively.The phytotoxic effects of all compounds were assayed on radish seedlings,gliricidin(3)and cyclo-(cis-4-hydroxy-D-prolyl-L-leucine(13)inhibited the root growth of radish(Raphanus sativus)seedlings at 100 ppm with inhibitory rates of 66.6% and 87.7%,respectively.5.Eleven metabolites 1-11 were isolated from the fermentation broth of Streptomyces sp.aw99 c.Compounds p-acetamidophenol(2),cyclo(Pro-Leu)(4),cyclo(Pro-Ala)(6),cyclo(Pro-Phe)(10)inhibited the Root growth of Lactuca sativa seedlings with inhibitory rates of 85%,65%,60%,55% at a concentration of 100 ppm.Compounds 2 and 4 inhibited the Hypocotyls growth of Lactuca sativa seedlings with inhibitory rates of 42%,35%,respectively.6.Six metabolites 1-6 were isolated from the fermentation broth of Streptomyces zinciresistens K42,including germicidin B(1),germicidin A(2),isogermicidin A(3).The phytotoxic effects of all compounds were assayed on Lactuca sativa seedlings,compounds1-3 inhibited the root growth of Lactuca sativa seedlings at 50 ppm.7.Seven metabolites 1-7 were isolated from the fermentation broth of Peltaster fructicola.Their structures were elucidated as :(E)-7-hydroxy-3,7-dimethylocta-1,5-dien-3-yl acetate(1),N-AcetyIdopamine(2),cyclo-(trans-4-hydroxy-L-prolylL-phenylalanine)(3),N-Acetyltyramine(4),N-(2-(1H-indol-3-yl)ethyl)propionamide(5),thymidine(6),and pyrrole-2-carboxylic acid(7).