Four New Xanthones from Cratoxylum cochinchinense and Their In Vitro Antiproliferative Effects

Abstract

The study of the chemical constituents of branches and twigs of Cratoxylum cochinchinense collected in Singapore led to the isolation and structural elucidation of four new xanthones, named cratoxanthone A (1), B (2), C (3), and D (4), together with six known xanthones (5–10) and one known dihydroanthracenone (11). Eight xanthones (including 1 and 2) and 11 were tested for their antiproliferative activity in three human carcinoma cell lines (lung adenocarcinoma A549, colorectal carcinoma Colo205, and epidermoid carcinoma KB) and a human acute lymphoblastic leukemia B cell line (NALM-6), and the mitochondrial membrane potential was determined in KB cells. New xanthones 1 and 2 attenuated NALM-6 cell proliferation with IC₅₀ values of 17.78 and 8.27 µM, respectively. Furthermore, KB cells treated with these compounds had significantly decreased mitochondrial membrane potentials. Notably, the proliferation of A549 cells was specifically inhibited by 11, but not the xanthones.

Key words

Cratoxylum cochinchinense - Hypericaceae - xanthones - dihydroanthracenone - antiproliferative activity

• References

• 1 Vo VV. A Dictionary of medicinal Plants in Vietnam. Ho Chi Minh City: Y Hoc Publisher; 1997
• 2 Burkill IH. A Dictionary of the economic Products of the Malay Peninsula. Kuala Lumpur, Malaysia: Ministry of Agriculture and Co-operatives on behalf of the Governments of Malaysia and Singapore; 1966: 1240
• 3 Tang SY, Whiteman M, Peng ZF, Jenner A, Yong EL, Halliwell B. Characterization of antioxidant and antiglycation properties and isolation of active ingredients from traditional chinese medicines. Free Radic Biol Med 2004; 36: 1575-1587
• 4 Tang SY, Whiteman M, Jenner A, Peng ZF, Halliwell B. Mechanism of cell death induced by an antioxidant extract of Cratoxylum cochinchinense (YCT) in Jurkat T cells: the role of reactive oxygen species and calcium. Free Radic Biol Med 2004; 36: 1588-1611
• 5 Rattanaburi S, Daus M, Watanapokasin R, Mahabusarakam W. A new bisanthraquinone and cytotoxic xanthones from Cratoxylum cochinchinense . Nat Prod Res 2014; 28: 606-610
• 6 Laphookhieo S, Maneerat W, Koysomboon S. Antimalarial and cytotoxic phenolic compounds from Cratoxylum maingayi and Cratoxylum cochinchinense . Molecules 2009; 14: 1389-1395
• 7 Raksat A, Sripisut T, Maneerat W. Bioactive xanthones from Cratoxylum cochinchinense . Nat Prod Commun 2015; 10: 1969-1972
• 8 Duangsrisai S, Choowongkomon K, Bessa LJ, Costa PM, Amat N, Kijjoa A. Antibacterial and EGFR-tyrosine kinase inhibitory activities of polyhydroxylated xanthones from Garcinia succifolia . Molecules 2014; 19: 19923-19934
• 9 Ren Y, Matthew S, Lantvit DD, Ninh TN, Chai H, Fuchs JR, Soejarto DD, de Blanco EJ, Swanson SM, Kinghorn AD. Cytotoxic and NF-κB inhibitory constituents of the stems of Cratoxylum cochinchinense and their semisynthetic analogues. J Nat Prod 2011; 74: 1117-1125
• 10 Azebaze AG, Meyer M, Valentin A, Nguemfo EL, Fomum ZT, Nkengfack AE. Prenylated xanthone derivatives with antiplasmodial activity from Allanblackia monticola STANER L.C. Chem Pharm Bull (Tokyo) 2006; 54: 111-113
• 11 Sakai S, Katsura M, Takayama H, Aimi N, Chokethaworn N, Suttajit M. The structure of garcinone E. Chem Pharm Bull (Tokyo) 1993; 41: 958-960
• 12 Iinuma M, Tosa H, Tanaka T, Asai F, Kobayashi Y, Shimano R, Miyauchi K. Antibacterial activity of xanthones from Guttiferaeous plants against methicillin-resistant Staphylococcus aureus . J Pharm Pharmacol 1996; 48: 861-865
• 13 Chitchumroonchokchai C, Thomas-Ahner JM, Li J, Riedl KM, Nontakham J, Suksumrarn S, Clinton SK, Kinghorn AD, Failla ML. Anti-tumorigenicity of dietary α-mangostin in an HT-29 colon cell xenograft model and the tissue distribution of xanthones and their phase II metabolites. Mol Nutr Food Res 2013; 57: 203-211
• 14 Shih YW, Chien ST, Chen PS, Lee JH, Wu SH, Yin LT. α-Mangostin suppresses phorbol 12-myristate 13-acetate-induced MMP-2/MMP-9 expressions via αvβ3 integrin/FAK/ERK and NF-κB signaling pathway in human lung adenocarcinoma A549 cells. Cell Biochem Biophys 2010; 58: 31-44
• 15 Ho CK, Huang YL, Chen CC. Garcinone E, a xanthone derivative, has potent cytotoxic effect against hepatocellular carcinoma cell lines. Planta Med 2002; 68: 975-979
• 16 Jung HA, Su BN, Keller WJ, Mehta RG, Kinghorn AD. Antioxidant xanthones from the pericarp of Garcinia mangostana (Mangosteen). J Agric Food Chem 2006; 54: 2077-2082
• 17 Wang JJ, Sanderson BJ, Zhang W. Cytotoxic effect of xanthones from pericarp of the tropical fruit mangosteen (Garcinia mangostana Linn.) on human melanoma cells. Food Chem Toxicol 2011; 49: 2385-2391
• 18 Mahabusarakam W, Nuangnaowarat W, Taylor WC. Xanthone derivatives from Cratoxylum cochinchinense roots. Phytochemistry 2006; 67: 470-474
• 19 Ito C, Itoigawa M, Mishina Y, Filho VC, Mukainaka T, Tokuda H, Nishino H, Furukawa H. Chemical constituents of Calophyllum brasiliensis: structure elucidation of seven new xanthones and their cancer chemopreventive activity. J Nat Prod 2002; 65: 267-272
• 20 Ito C, Mishina Y, Litaudon M, Cosson JP, Furukawa H. Xanthone and dihydroisocoumarin from Montrouziera sphaeroidea . Phytochemistry 2000; 53: 1043-1046
• 21 Daud SB, Ee GC, Malek EA, Teh SS, See I. A new coumarin from Calophyllum hosei . Nat Prod Res 2014; 28: 1534-1538
• 22 Gunasekera SP, Sultanbawa MUS, Balasubramaniam S. Mangostin from the barks of Hydnocarpus species. Phytochemistry 1973; 12: 232-233
• 23 Suksamrarn S, Suwannapoch N, Ratananukul P, Aroonlerk N, Suksamrarn A. Xanthones from the green fruit hulls of Garcinia mangostana . J Nat Prod 2002; 65: 761-763
• 24 Itoigawa M, Ito C, Tokuda H, Enjo F, Nishino H, Furukawa H. Cancer chemopreventive activity of phenylpropanoids and phytoquinoids from Illicium plants. Cancer Lett 2004; 214: 165-169
• 25 Cory AH, Owen TC, Barltrop JA, Cory JG. Use of an aqueous soluble tetrazolium/formazan assay for cell growth assays in culture. Cancer Commun 1991; 3: 207-212
• 26 Cossarizza A, Baccarani-Contri M, Kalashnikova G, Franceschi C. A new method for the cytofluorimetric analysis of mitochondrial membrane potential using the J-aggregate forming lipophilic cation 5,5′,6,6′-tetrachloro-1,1′,3,3′-tetraethylbenzimidazolcarbocyanine iodide (JC-1). Biochem Biophys Res Commun 1993; 197: 40-45
• 27 Zhang X, Li X, Ye S, Zhang Y, Tao L, Gao Y, Gong D, Xi M, Meng H, Zhang M, Gao W, Xu X, Guo Q, You Q. Synthesis, SAR and biological evaluation of natural and non-natural hydroxylated and prenylated xanthones as antitumor agents. Med Chem 2012; 8: 1012-1025
• 28 Laphookhieo S, Syers JK, Kiattansakul R, Chantrapromma K. Cytotoxic and antimalarial prenylated xanthones from Cratoxylum cochinchinense . Chem Pharm Bull (Tokyo) 2006; 54: 745-747