Synthesis and mitochondrial complex I inhibition of dihydroxy-cohibin A, non-THF annonaceous acetogenin analogue

Hiroyuki Konno; Naoki Hiura; Hidefumi Makabe; Masato Abe; Hideto Miyoshi

doi:10.1016/j.bmcl.2003.11.057

Synthesis and mitochondrial complex I inhibition of dihydroxy-cohibin A, non-THF annonaceous acetogenin analogue

Bioorg Med Chem Lett. 2004 Feb 9;14(3):629-32. doi: 10.1016/j.bmcl.2003.11.057.

Authors

Hiroyuki Konno¹, Naoki Hiura, Hidefumi Makabe, Masato Abe, Hideto Miyoshi

Affiliation

¹ Department of Biological Science and Technology, Faculty of Engineering, University of Tokushima, 2-1Minamijosanjima-cho, Tokushima 770-8506, Japan. [email protected]

PMID: 14741257
DOI: 10.1016/j.bmcl.2003.11.057

Abstract

To elucidate the inhibitory action of acetogenins, we synthesized an acetogenin derivative which possesses tetraol in place of the tetrahydrofuran ring and examined its inhibitory activity against bovine heart mitochondrial complex I. Our results indicate that these hydroxy groups are an essential structural factor though it is not effective as bis-THF hydroxy groups combination.

MeSH terms

Acetogenins
Animals
Cattle
Electron Transport Complex I / antagonists & inhibitors*
Enzyme Inhibitors / chemistry
Enzyme Inhibitors / pharmacology
Fatty Alcohols / chemical synthesis*
Fatty Alcohols / pharmacology*
Furans / chemical synthesis*
Furans / chemistry
Furans / pharmacology*
Hydroxides / chemistry
Lactones / chemical synthesis*
Lactones / pharmacology*
Mitochondria, Heart / enzymology*
Molecular Structure
Structure-Activity Relationship
Submitochondrial Particles / enzymology

Substances

Acetogenins
Enzyme Inhibitors
Fatty Alcohols
Furans
Hydroxides
Lactones
hydroxide ion
Electron Transport Complex I