New Cytotoxic Prenylated Isoflavonoids from Bituminaria morisiana

Abstract

Using cytotoxicity against KB cancer cells as a lead, bioguided-fractionation of the petroleum ether and ethyl acetate extracts of Bituminaria morisiana leaves led to the isolation of two new pterocarpans, namely 3,9-dihydroxy-4-(3,3-dimethylallyl) [6aR, 11aR]-pterocarpan, 3-hydroxy-4-(3,3-dimethylallyl)-4′′,5′′-dehydropyrano[8,9:2′′,3′′][6aR,11aR]-pterocarpan and one new isoflavone identified as 4′,5′′-dihydroxy-6′′-methoxy-4′′,4′′-dimethyl-4′′,5′′-dihydro-6′′H-pyrano[2′′,3′′:7,8]-isoflavone. Moreover, two known pterocarpans, erybraedin C and bitucarpin A, three known isoflavones, daidzein, 8-prenyldaidzein and bidwillon C, one known furocoumarin, pseudoisopsoralen and one known coumestan, coumestrol were isolated. The structures of the isolated compounds were established by means of 1D and 2D NMR spectroscopy, as well as mass spectrometry. Further cytotoxicity tests against cells related to the immune system (Jurkat T, Mono-Mac-6 and polymorphonuclear cells) showed a moderate activity of the known pterocarpan erybraedin C against all cell lines used (IC₅₀ values between 17.6 - 28.8 μM). In addition, erybraedin C was found to induce necrosis in leukaemia Jurkat T cells.

Bituminaria morisiana - Fabaceae - pterocarpans - isoflavones - cytotoxicity - necrosis

References

• 1 Murray R DH, Méndez J, Brown S A. The Natural Coumarins. Occurrence, Chemistry and Biochemistry. Chichester; John Wiley & Sons Ltd 1982: pp 291-322
• 2 Takhtajan A. Diversity and Classification of Flowering Plants. New York; Columbia University Press 1997
• 3 Pignatti S. Flora d’Italia. Vol. 2 Edagricole Bologna; 1982: pp 668-9
• 4 Pistelli L, Noccioli C, Appendino G, Bianchi F, Sterner O, Ballero M. Pterocarpans from Bituminaria morisiana and Bituminaria bituminosa .  Phytochemistry. 2003;  64 595-8
• 5 Gertsch J, Güttinger M, Sticher O, Heilmann J. Relative quantification of mRNA levels in Jurkat T cells with RT - real time - PCR: New possibilities for the screening of anti-inflammatory and cytotoxic natural compounds.  Pharmaceutical Research. 2002;  19 1235-42
• 6 Heilmann J, Wasescha M R, Schmidt T J. The influence of glutathione and cysteine levels on the cytotoxicity of helenanolide type sesquiterpene lactones against KB cells.  Bioorganic and Medicinal Chemistry. 2001;  9 2189-94
• 7 Koopman G, Reutelingsperger C P, Kuijten G A, Keehnen R M, Pals S T, van Oers M H. Annexin V for flow cytometric detection of phosphatidylserine expression on B cells undergoing apoptosis.  Blood. 1994;  84 415-20
• 8 Gertsch J, Sticher O, Schmidt T J, Heilmann J. Influence of helenanolide-type sesquiterpene lactones on gen transcription profiles in Jurkat T-cells and human peripheral blood cells: Anti-inflammatory and cytotoxic effects.  Biochemical Pharmacology. 2003;  66 2141-53
• 9 Dewick P M. The Flavonoids: Advances in Research Since 1986. ed. by Harborne JB London; Chapman and Hall 1994: p 167
• 10 Mabry T J, Markham K R, Thomas M B. The Systematic Identification of Flavonoids. New York; Springer 1970
• 11 Markham K R. Techiques of Flavonoids Identification. London; Academic Press 1982: pp 36-51
• 12 Tahara S, Ingham J L, Nakahara S, Mizutani J, Harborne J B. Fungitoxic dihydrofuranoisoflavones and related compounds in white lupin, Lupinus albus .  Phytochemistry. 1984;  23 1899-900
• 13 Murray R DH, Sutcliffe M, McCabe P H. Claisen rearrangements - IV oxidative cyclisation of two coumarin O-isoprenylphenols.  Tetrahedron. 1971;  27 4901-6
• 14 Mitscher L A, Okwute K, Sitaraghav R, Gollapudi S R, Drake S, Avona E. Antimicrobial pterocarpans of nigerian Erythrina mildbraeii .  Phytochemistry. 1988;  27 3449-52
• 15 Agrawal P K. Carbon-13 NMR of flavonoids. Elsevier Amsterdam; 1989
• 16 Munekazu I, Tanaka T, Misuno M, Yamamoto H, Kobayashi Y, Yonemori S. Phenolic constituents in Erythrina x bidwilli and their activity against oral microbial organisms.  Chemical and Pharmaceutical Bulletin. 1992;  40 2749-52
• 17 Iinuma M, Okawa Y, Tanaka T, Kobayashi Y, Miyauchi K. Phenolic compounds in Erythrina x bidwilli and their activity against oral microbial organisms.  Heterocycles. 1994;  39 687-92
• 18 Manzini P, Rodighiero P, Chilin A, Guiotto A. ¹H-NMR spectra of variously annulated furocoumarins.  Magnetic Resonance in Chemistry. 1985;  23 875-6
• 19 Guiotto A, Manzini P, Chilin A, Pastorini G, Rodighiero P. ¹³C-NMR and carbon-proton constants of variously annulated furocoumarins.  Journal of Heterocyclic Chemistry. 1985;  22 649-56
• 20 Kraus G , Zhang N. Hydrogen-atom abstraction/cyclization in synthesis. Direct syntheses of coumestan and coumestrol.  Journal of Organic Chemistry. 2000;  65 5644-6