Isolation and Chemical Transformation of Fungal Metabolites, Pseurotin A and Fumiquinazoline C and Their Biological Activities

Abstract

Isolation and Chemical Transformation of Fungal Metabolites, Pseurotin A and Fumiquinazoline C， and Their Biological Activities

ZHILE FENG

Department of Chemistry, The Graduate School, Pukyong National University,

Abstract

Marine microorganisms have become an important source for producing pharmacologically active metabolites.

In our investigation for bioactive natural products, the marine-derived fungi were selected as our targets for chemical research. The secondary metabolites were obtained from combining the modern knowlwdge of microorganism and chemical techniques in culture, extraction, isolation, and purification. The total structure of secondary metabolites,chemical transformation of them and their biological activities have been investigated, and the results are as following:

1. Pseurotin-A (1) have been isolated from the culture broth of the marine-derived fungus Aspergillus fumigatus. (MFA149). The structure and absolute stereochemistry of the compounds were assigned by spectroscopic methods. Compounds 1 exhibited a significant radical scavenging activity against 1,1― diphenyl-2-picrylhydrazyl (DPPH) with IC50 values of 17.9┢M, respectively, which was more active than the positive control, L-ascorbic acid (IC50, 20┢M). and also exhibited in vitro mild antibacterial activity against methicillin resistant Staphylococcus aureus (MRSA) and multidrug-resistant S. aureus (MDRSA) with MIC value of 12.5 ┢g/mL, respectively.

Pseurotin-A (1) 2. Fumiquinazoline C (2) have been isolated from the culture broth of the marine-derived fungus Aspergillus fumigatus. (MFA149). The planar structure was elucidated on the basis of COSY, HMQC, and HMBC correlations. Compound 2 exhibited the DPPH scavenging activity with IC50 value of 18.3 ┢M, which is more active than the positive control L-ascorbic acid (IC50 20 ┢M);

Fumiquinazoline C (2)

3. Chemical transformation of Pseurotin A led to the production of Pseurotin A-Br1(3) and Pseurotin A-Br2(4) which showed in vitro mild antibacterial activity against methicillin resistant Staphylococcus aureus (MRSA) and multidrug-resistant S. aureus (MDRSA) with MIC value of 16.8┢g/mL and 6.25┢g/mL, respectively.They also exhibited significant radical scavenging activity against DPPH with IC50 value of 10.0 ┢M and 13.9┢M more than the positive control L-ascorbic acid (IC50 20 ┢M);

Pseurotin A Br1 (3)

Pseurotin A Br2 (4)