Bioactive Chaetoglobosins from the Mangrove Endophytic Fungus Penicillium chrysogenum

Abstract

A novel chaetoglobosin named penochalasin I (<b>1</b>) with a unprecedented six-cyclic 6/5/6/5/6/13 fused ring system, and another new chaetoglobosin named penochalasin J (<b>2</b>), along with chaetoglobosins G, F, C, A, E, armochaetoglobosin I, and cytoglobosin C (<b>3</b>-<b>9</b>) were isolated from the culture of <i>Penicillium chrysogenum</i> V11. Their structures were elucidated by 1D, 2D NMR spectroscopic analysis and high resolution mass spectroscopic data. The absolute configuration of compounds <b>1</b> and <b>2</b> were determined by comparing the theoretical electronic circular dichroism (ECD) calculation with the experimental CD. Compound <b>1</b> was the first example, with a six-cyclic fused ring system formed by the connection of C-5 and C-2' of the chaetoglobosin class. Compounds <b>5</b>-<b>8</b> remarkably inhibited the plant pathogenic fungus <i>R. solani</i> (minimum inhibitory concentrations (MICs) = 11.79-23.66 μM), and compounds <b>2</b>, <b>6</b>, and <b>7</b> greatly inhibited <i>C. gloeosporioides</i> (MICs = 23.58-47.35 μM), showing an antifungal activity higher than that of carbendazim. Compound <b>1</b> exhibited marked cytotoxicity against MDA-MB-435 and SGC-7901 cells (IC₅₀ < 10 μM), and compounds <b>6</b> and <b>9</b> showed potent cytotoxicity against SGC-7901 and A549 cells (IC₅₀ < 10 μM).