Circumdatin H, a New Inhibitor of Mitochondrial NADH Oxidase, from Aspergillus ochraceus

Abstract

Circumdatin H (1), a new alkaloid from the culture broth of Aspergillus ochraceus, has been isolated, together with a known circumdatin, circumdatin E (2) and other known compounds: flavacol (3) and stephacidin A (4). The structure of 1 was established on the basis of chemical and spectral evidence. All of these alkaloids showed biological activity as inhibitors of the mammalian mitochondrial respiratory chain.

Enterotoxicity of a nonribosomal peptide causes antibiotic-associated colitis

“…Values are means ± SEM, two-tailed Student t test. *P < 0.05. the exception of pentacyclic PBDs that have been isolated from marine Aspergilli (44,45). The origin of the genomic island carrying the tilivalline biosynthetic genes would thus seem to be phylogenetically distant.…”

Circumdatin I, a New Ultraviolet-A Protecting Benzodiazepine Alkaloid from a Marine Isolate of the Fungus Exophiala

“…[3ϳ6], epi-aszonalenins AϳC [7], benzodiazepinedione [8], and asperlicins [9], were widespread microbial products commonly found in nutrient rich cultures of both terrestrial and marine fungi, and exhibited interesting biological activities, treatment of gastrointestinal and CNS disorder [5,9], inhibition of mitochondrial NADH oxidase [6], and psychoactive properties [7]. Circumdatins AϳH have been previously isolated from Aspergillus ochraceus and have been suggested as good chemotaxonomic markers for this species [3ϳ6].…”

First Total Synthesis of (-)-Circumdatin H, a Novel Mitochondrial NADH Oxidase Inhibitor

“…4 Related alkaloids have been isolated from a terrestrial isolate of the fungus Aspergillus ochraceus. Circumdatin C (3) 5 and circumdatin F (4) 6 are prototypical members, while other members such as circumdatin D (5), 6 circumdatin E (6) 6 and circumdatin H (7) 7 have an additional tetrahydropyrrole ring ( Figure 1). The compounds of this group are considered to be useful chemotaxonomic markers.…”

“…The compounds of this group are considered to be useful chemotaxonomic markers. Among these compounds, circumdatin H (7) and circumdatin E (6) are able to inhibit the mitochondrial respiratory chain in submitochondrial particles from beef heart, presumably by interfering with NADH oxidase activity (IC 50 1.5 mM and 2.5 mM, respectively). Similar molecules, circumdatins A-H, have recently been reported by Kusumi and co-workers from the marine-derived fungus Aspergillus ostianus strain 01F313, together with a new compound, named circumdatin J (8), and a revision of the structures of circumdatin A and B from the previously reported betaine structures to unique oxepinones based on X-ray crystallography.…”