Pubescenes, Jatrophane Diterpenes, from Euphorbia pubescens, with Multidrug Resistance Reversing Activity on Mouse Lymphoma Cells

Abstract

The macrocyclic jatrophane diterpene polyesters, pubescenes A - D (1 - 4) were isolated from the whole dried plant of Euphorbia pubescens, and evaluated for multidrug resistance (MDR) reversing activity on mouse lymphoma cells. All the compounds displayed very strong activity compared with the positive control verapamil. Pubescene D (4) is a new compound, whose structure was established as 3β,9α,-diacetoxy-7β-benzoyloxy-15β-hydroxy-14-oxo-2βH-jatropha-5E,12E-diene by spectroscopic methods, including ¹H-¹H COSY, HMQC, HMBC and NOESY.

References

• 1 Appendino G, Jakupovic S, Tron G C, Jakupovic J, Milon V, Ballero M. Macrocyclic diterpenoids from Euphorbia semiperfoliata .  J Nat Prod. 1998;  61 749-56
• 2 Hohmann J, Molnár J, Rédei D, Evanics F, Forgo P, Kálmán A, Argay G, Szabó P. Discovery and biological evaluation of a new family of potent modulators of multidrug resistance: reversal of multidrug resistance of mouse lymphoma cells by new natural jatrophane diterpenoids isolated from Euphorbia species .  J Med Chem. 2002;  45 2425-31
• 3 Kim S E, Hong Y S, Kim Y C, Lee J J. Mode of action of torilim in multidrug-resistance cancer cell lines.  Planta Med. 1998;  64 335-8
• 4 Wiese M, Pajeva I K. Structure-activity relationships of multidrug resistance reversers.  Curr Med Chem. 2001;  8 685-713
• 5 Valente C, Ferreira M JU, Abreu P M, Pedro M, Cerqueira F, Nascimento M SJ. Three new jatrophane-type diterpenes from Euphorbia pubescens .  Planta Med. 2003;  69 361-6
• 6 Seip E H, Hecker E. Derivatives of characiol, macrocyclic diterpene esters of the jatrophane type from Euphorbia characias .  Phytochemistry. 1984;  23 1689-94
• 7 Yamamura S, Yoshikazu S, Kosemura S, Ohtsuka J, Tayama T, Ohba S, Ito M, Saito Y, Terada Y. Diterpenes from Euphorbia helioscopia .  Phytochemistry. 1989;  28 3421-36
• 8 Lieu L G, Tan R X. New jatrophane diterpenoid esters from Euphorbia turczaninowii .  J Nat Prod. 2001;  64 1064-68 and related references cited therein
• 9 Hohmann J, Vasas A, Günther G, Máthé I, Evanics F, Dombi G, Jerkovitch G. Macrocyclic diterpene polyesters of the jatrophane type from Euphorbia esula .  J Nat Prod. 1997;  60 331-5
• 10 Ferreira M JU, Madureira A M, Ascenso J R. A tetracyclic diterpene and triterpenes from Euphorbia segetalis .  Phytochemistry. 1998;  49 179-83
• 11 Yamamura S, Kosemura S, Ohba S, Ito M, Saito Y. The isolation and structures of Euphoscopins A and B.  Tetrahedron Lett. 1981;  22 5315-18
• 12 Szabó D, Keyzer H, Kaiser H E, Molnár J. Reversal of multidrug resistance of tumor cells.  Anticancer Res. 2000;  20 4261-74
• 13 Cornwell M M, Pastan I, Gottesmann M M. Certain calcium channel blockers bind specifically to multidrug-resistance human KB carcinoma membrane vesicles and inhibit drug binding to P-glycoprotein.  J Biol Chem. 1987;  262 2166-70
• 14 Hershey P B, Cruinkehank C ND, Mullins L I. The quantitative reduction of 2,3,5-triphenyltetrazolium chloride by skin in vitro .  J Hiostochem Cytochem. 1958;  6 191-6
• 15 Weaver J L, Szabo G, Pine P S, Gottesman M M, Goldenberg S, Aszalos A. The effect of ion channel blockers, immunosuppressive agents, and other drugs on the activity of the multidrug transporter.  Int J Cancer. 1993;  54 456-61
• 16 Kessel D. Exploring multidrug resistance using Rhodamine 123.  Cancer Commun. 1989;  1 145-9