Investigation On The Secondary Metabolites And Their Bioactivities Of Penicillium Sp.W1-1 And Epicoccum Sorghinum W69-2

Antibiotics have been clinically playing key roles in treating infectious and antitumor diseases.However,drug-resistance has greatly reduced the effect of antibiotics.Pharmaceutical companies have lost their interest in discovering novel antibiotics because of long period and low return on huge investment.Discovering novel chemicals from different bio-niches is the main method to solve drug-resistant infections.Thus,in this thesis,we tried to find active molecules for antimicroorganisms from our fungal library.The fraction from the culture of a soil-derived fungus Penicillium sp.W1-1 presented better in vivo anti-pathogenic activities in mice than the positive drug berberine.Sixteen compounds were isolated and identified as 6-hydroxy-cyclopiamine B（1）,paspaline（2）,PC-M5’（3）,4a-demethyl-paspaline-4a-carboxylic acid（4）,drechmerin A（5）,（3β,22E）-ergosta-5,7,22-trien-3-ol（6）,5,8-epidioxy-（3β,5α,8α,22E）-ergosta-6,9,22-trien-3-ol（7）,（22E,24R）-ergosta-7,22-diene-3β,5α,6β-triol（8）,brefeldin A（9）,7’-O-acetyl-brefeldin A（10）,chaetosemin J（11）,3α,11,15-trihydroxy-drimene（12）,4-hydroxy-3,6-dimethyl-2H-pyran-2-one（13）,2,4-dihydro-lH-indan-trans-1,2-diol（14）,（S）-5-ethyl-8,8-dimethyl nonanal（15）and（Z）-9-eicosenoic acid（16）.Chemical investigaiton on Epicoccum sorghinum W69-2,another soil-derived fungal isolates resulted in 10 pure compounds which were identified as m-hydroxybenzyl alcohol（17）,parasitenone（18）,decarestrictine F（19）,2-（hydroxymethyl）benzene-1,4-diol（20）,2-hydroxy-6-methylbenzoic acid A（21）,3,4-dihydroxy-benzaldehyde（22）,2-methyl-1,4-benzenediol（23）,3-hydroxy-5-methybenzoic acid（24）,3-hydroxybenzoic acid（25）and 2-（methoxymethyl）benzene-1,4-diol（26）.Compounds 2,4 and 5 presented moderate antimicrobial activity with MICs ranged from 12.5 μg/mL to 25 μg/mL.The anti-microbial activity of 4 was reported for the first time.Tests were carried out against one pathogenic fungus,two G-bacteria and five G+bacteria.The MICs ranged from 25 μg/mL to 50 μg/mL.The results showed that 4 presented broad-spectrum antimicrobial activities and without cytotoxity for mammalian cells,could inhibit growth of drug-resistant pathogenic strains Escherichia coli and Candida albicans with post-contact effect（PCE）,changed the morphology and membrane structure,killed cells with leakage,could eradicate the biofilms of C.albicans.