Jatrophane Diterpenes from the Latex of Euphorbia obtusifolia with Inhibitory Activity on the Mammalian Mitochondrial Respiratory Chain

Abstract

Seven diterpenes isolated of the latex of the Euphorbia obtusifolia were evaluated as inhibitors of the NADH oxidase activity in submitochondrial particles from bovine heart. Compound 2, 2,3,5,7,8,9,15-heptahydroxyjatropha-6(17),11-diene-14-one 8,9-diacetate 7-isobutyrate 2,3-bis(2-methylbutyrate), was the most potent inhibitor with an inhibitory concentration (IC₅₀) value of 5.1 ± 0.2 μM. In the present study, some structure-activity trends are suggested for the inhibitory activity of these natural products on the mammalian mitochondrial respiratory chain.

References

• 1 Hohmann J, Evanics F, Dombi G, Szabó P. Euphosalicin, a new diterpene polyester with multidrug resistance reversing activity from Euphorbia salicifolia .  Tetrahedron. 2001;  57 211-5
• 2 Taylor M D, Smith A B, Furst G T, Gunasekara S P, Bevelle C A. New antileukemic jatrophone derivatives from Jatropha gossypiifolia: Structural and stereochemical assignment through nuclear magnetic resonance spectroscopy.  J Am Chem Soc. 1983;  105 3177-83
• 3 Kupchan S M, Sigel C W, Matz M J, Gilmore C J, Bryan R F. Structure and stereochemistry of jatrophone, a novel macrocyclic diterpenoid tumor inhibitor.  J Am Chem Soc. 1976;  98 2295-300
• 4 D’Alagni M, De Petris M, Marini-Bettolo G B. On the interaction between jatrophone and DNA.  FEBS Lett. 1981;  136 175-9
• 5 Lillehaug J R, Kleppe K, Sigel C W, Kupchan S M. Reaction of biological thiols with the tumor inhibitor jatrophone. Inhibition of RNA polymerase.  Biochim Biophys Acta. 1973;  327 92-100
• 6 Marchetti P, Hirsch T, Zamzami N, Castedo M, Decaudin D, Susin S A, Masse B, Kroemer G. Mitochondrial permeability transition triggers lymphocyte apoptosis.  J Immunol. 1996;  157 4830-6
• 7 Zoratti M, Szabo I. The mitochondrial permeability transition.  Biochim Biophys Acta. 1995;  1241 139-76
• 8 Marco J A, Sanz-Cervera J F, Checa J, Palomares E, Fraga B M. Jatrophane and tigliane diterpenes from the latex of Euphorbia obtusifolia .  Phytochemistry. 1999;  52 479-85
• 9 Degli E M, Ghelli A, Ratta M, Cortes D, Estornell E. Natural substances acetogenins from the family Annonaceae are powerful inhibitors of mitochondrial NADH dehydrogenase (complex I).  Biochem J. 1994;  301 161-7
• 10 Noack E A, Crea A E, Falsone G. Inhibition of mitochondrial oxidative phosporylation by 4-deoxyphorbol triester, a poisonous constituent of the latex sap of Euphorbia biglandulosa Desf.  Toxicon. 1980;  18 165-74
• 11 Marco J A, Sanz-Cervera J F, Ropero F J, Fraga B M. Ingenane and lathyrane diterpenes from the latex of Euphorbia acrurensis .  Phytochemistry. 1998;  49 1095-9
• 12 Marco J A, Sanz-Cervera J F, Yuste A. Ingenane and lathyrane diterpenes from the latex of Euphorbia canariensis .  Phytochemistry. 1997;  45 563-70