Azaphilone molecules from freshwater derived fungi

Abstract

Ovarian cancer is the most lethal gynecological malignancy and the fifth leading cause of cancer death among women. This high mortality rate is due to difficult detection, unclear symptoms, and an absence of known precursor lesions. In addition, tumors that are initially responsive to chemotherapeutics often become resistant. Thus, discovery of novel drug leads for ovarian cancer treatment is of paramount importance. To address this need, our lab focuses on secondary metabolites produced by microorganisms in the aquatic environment as a source for new therapeutic leads. In particular, freshwater-derived fungi remain largely uninvestigated for novel chemical scaffolds. Hence, there is untapped potential in this environment for structural uniqueness. In the current study, a fraction library of secondary metabolites produced by freshwater-derived fungi were screened for potential selective toxicity against chemo-resistant ovarian cancer cells. Two new molecules of the azaphilone class have been identified from fungal strain FJ015 in Lake Huron. Herein, we report the structure elucidation of these metabolites by analysis of one- and two-dimensional nuclear magnetic resonance spectroscopy and high-resolution mass spectrometry. Details of the biological activity of these molecules will also be discussed.