New Azaphilones and Chlorinated Phenolic Glycosides from Chaetomium elatum with Caspase-3 Inhibitory Activity

Abstract

Three new azaphilones, chaetomugilin S (1), 7,5′-bis-epi-chaetoviridin A (2), and 7-epi-chaetoviridin E (3), and two new chlorinated phenolic glycosides, globosumoside A (4) and globosumoside B (5), were isolated from the crude extract of the fungal strain Chaetomium elatum No. 89–1–3–1. Their structures were determined by detailed NMR and MS spectroscopic analyses. The absolute configurations of C-7 in chaetomugilin S (1), 7,5′-bis-epi-chaetoviridin A (2), and 7-epi-chaetoviridin E (3) were assigned by CD experiments, and the absolute configurations of 1 and 2 were established by X-ray crystallography. Compounds 1–3 are the first examples of 7R-configurated azaphilones with a chlorinated isochromen from Chaetomium spp. In addition, compounds 1–3 showed inhibitory activity in the cysteine aspartyl-specific protease-3 (caspase-3) enzymatic assay, with IC₅₀ values of 20.6, 10.9, and 7.9 µM, respectively.

Key words

Chaetomium elatum - Chaetomiaceae - azaphilones - chlorinated phenolic glycosides - caspase-3 inhibitors

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