Guanaconetins, new antitumoral acetogenins, mitochondrial complex I and tumor cell growth inhibitors.

The antitumoral activity of a series of acetylated bis-tetrahydrofuranic acetogenins with a threo/trans/threo/trans/erythro relative configuration was characterized by four new natural and two semisynthetic, 15,24,30-trioxygenated acetogenins that were found to inhibit mitochondrial complex I enzyme as well as growth of several tumor cell lines. Placement of acetyl groups along the alkyl chain modulated the potency of the bis-tetrahydrofuranic acetogenins and could be important for future utilization of these compounds as chemotherapeutic agents.

Novel inhibitors of the mitochondrial respiratory chain: oximes and pyrrolines isolated from Penicillium brevicompactum and synthetic analogues.

The capacity of inhibition of the mammalian mitochondrial respiratory chain of brevioxime 5a, a natural insecticide compound isolated from Penicillium brevicompactum culture broth, and another 15 analogue compounds, other oximes 5b and 5c; two diastereomeric pyrrolidines 1c' and 1c' '; five pyrrolines 3c', 3c' ' (diastereomers between them), 3a, 3b, and 6; two oxazines 4c' and 4c' ' (also diastereomers between them); and four pyrrol derivatives 7-10, are analyzed in this paper. Compounds 3b, 3c', 3c' ', 4c', 4c' ', 5b, 5c, 6, and 10 were found to be inhibitors of the integrated electron transfer chain (NADH oxidase activity) in beef heart submitochondrial particles (SMP), establishing that all of them except compound 3b and 6 only affected to complex I of the mitochondrial respiratory chain. The most potent product was 5b, with an IC50 of 0.

Circumdatin H, a new inhibitor of mitochondrial NADH oxidase, from Aspergillus ochraceus.

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.

Acetogenins from Annonaceae: recent progress in isolation, synthesis and mechanisms of action.

The aim of the present review is to summarise the knowledge about newly isolated acetogenins (ACGs) in the last six years. It will also report the total syntheses that have allowed either the confirmation or the revision of some structures, together with the biological activities and mechanism of action of such interesting natural products. In fact, of the 417 isolated compounds reviewed, over 176 have been added during the period from 1998 to 2004.

Bisbenzyltetrahydroisoquinolines, a new class of inhibitors of the mitochondrial respiratory chain complex I.

Four bisbenzyltetrahydroisoquinoline alkaloids (-)-medelline, (+)-antioquine, (+)-aromoline, and (+)-obamegine were isolated from the fruits of Xylopia columbiana. These compounds, the previously isolated alkaloids (+)-thaligrisine and (+)-isotetrandrine, as well as their O-acetylated derivatives were assayed on submitochondrial particles from beef heart as inhibitors of the mammalian respiratory chain. The results revealed that these alkaloids act as selective inhibitors of mitochondrial complex I in a 0.