Structure of Kaurane-Type Diterpenes from Parinari sprucei and their Potential Anticancer Activity

Abstract

Twenty-three kaurane-type diterpenes 1 - 23, including twenty new natural products 1 - 20, have been isolated from the leaves of Parinari sprucei and their structures elucidated by spectroscopic and chemical analysis. The isolated compounds were tested for their cytotoxic activity towards a panel of cancer cell lines. Compounds 9 and 10 showed activity against all cell lines with ED₅₀ values in the range of 10 - 20 μg/mL. The previously known 13-hydroxy-15-oxozoapatlin 21 was evaluated in an in vivo hollow fiber test, and found to be active with KB and LNCaP cells at the concentrations used.

Key words

Parinari sprucei - Chrysobalanaceae - leaves - kaurane diterpenes - cytotoxicity - hollow fiber test

References

• 1 Toledo C L, Kubitzki K, Prance G H. Flora de Venezuela. Vol. IV Ediciones Fundación Educación Ambiental Caracas; 1982: 411
• 2 Lee I S, Shamon L A, Chai H B, Chagwedera T E, Besterman J M, Farnsworth N R. et al . Cell-cycle specific cytotoxicity mediated by rearranged ent-kaurene diterpenoids isolated from Parinari curatellifolia .  Chem-Biol Interact. 1996;  99 193-204
• 3 Garo E, Maillard M, Hostettmann K, Stoeckli-Evans H, Mavi SS. Absolute configuration of a diterpene from Parinari capensis .  Helv Chim Acta. 1997;  80 538-44
• 4 Uys A CU, Malan S F, van Dyk S, van Zyl R L. Antimalarial compounds from Parinari capensis .  Bioorg Med Chem Lett. 2002;  12 2167-9
• 5 Braca A, Bader A, Morelli I, Scarpato R, Turchi G, Pizza C. et al . New pregnane glycosides from Caralluma negevensis .  Tetrahedron. 2002;  58 5837-48
• 6 Boger D L, Hikota M, Lewis B M. Determination of the relative and absolute stereochemistry of fostriecin (CI-920).  J Org Chem. 1997;  62 1748-53
• 7 Likhitwitayawuid K, Angerhofer C K, Cordell G A, Pezzuto J M. Traditional medicinal plants of Thailand. XX. Cytotoxic and antimalarial bisbenzylisoquinoline alkaloids from Stephania erecta .  J Nat Prod. 1993;  56 30-8
• 8 Seo E K, Kim N C, Mi Q, Chai H, Wall M E, Wani M C. et al . Macharistol, a new cytotoxic cinnamylphenol from the stems of Machaerium aristulatum .  J Nat Prod. 2001;  64 1483-5
• 9 Hollingshead M G, Alley M C, Camalier R F, Abbott B J, Mayo J G, Malspeis L. et al . In vivo cultivation of tumor cells in hollow fibers.  Life Sci. 1995;  57 131-41
• 10 Mi QQ, Lantvit DD, Reyes-Lim EE, Chai HH, Zhao WW, Lee I S. et al . Evaluation of the potential cancer chemotherapeutic efficacy of natural product isolates employing in vivo hollow fiber test.  J Nat Prod. 2002;  65 842-50
• 11 Waller D P, Zaneveld L JD, Fong H HS. In vitro spermicidal activity of gossypol.  Contraception. 1980;  22 183-7
• 12 Gu Z M, Fang X P, Zeng L, Kozlowski J F, McLaughlin J L. Novel cytotoxic annonaceous acetogenins: (2,4-cis and trans)-bulladecinones from Annona bullata (Annonaceae).  Bioorg Med Chem Lett. 1994;  4 473-8
• 13 Yamasaki K, Kohda H, Kobayashi T, Kasai R, Tanaka O. Structures of Stevia diterpene-glucosides: application of ¹³C NMR. Tetrahedron Lett 1976: 1005-7
• 14 Chen C Y, Chang F R, Cho C P, Wu Y C. Ent-kaurane diterpenoids from Annona glabra .  J Nat Prod. 2000;  63 1000-3
• 15 Wu Y C, Hung Y C, Chang F R, Cosentino M, Wang H K, Lee K H. Identification of ent-16β,17-dihydroxykauran-19-oic acid as an anti-HIV principle and isolation of the new diterpenoids annosquamosins A and B from Annona squamosa .  J Nat Prod. 1996;  59 635-7
• 16 Grande M, Moran J R, Macias M J, Macheño B. Carbon-13 nuclear magnetic resonance spectra of some tetracyclic diterpenoids isolated from Elaeselinum species.  Phytochem Anal. 1993;  4 19-24
• 17 Rundle N T, Xu L, Andersen R J, Roberge M. G2 DNA damage checkpoint inhibition and antimitotic activity of 13-hydroxy-15-oxozoapatlin.  J Biol Chem. 2001;  276 48 231-6