Alkyl Phloroglucinol Derivatives from Syzygium levinei and their Differentiation-Inducing Activity

Abstract

Eleven compounds have been identified from the whole plants of Syzygium levinei (Myrtaceae) on the basis of spectroscopic analysis and chemical methods. Among these compounds, (Z)-1-(2,6-dihydroxy-4-methoxyphenyl)-oct-5-en-1-one (1), (3E,7Z)-1-(2,6-dihydroxy-4-methoxyphenyl)-deca-3,7-dien-1-one (2), and 1-(2-O-β-D-glucopyranosyl-5,6-dihydroxy-4-methoxyphenyl)-octan-1-one (3) were characterized as new alkyl phloroglucinol derivatives, and 1-(2,6-dihydroxy-4-methoxyphenyl)-hexan-1-one (4) was identified as a new natural product. Compounds 1, 2, and 4 were found to inhibit the proliferation of leukemia K562 and HL-60 cells and also to induce the differentiation of K562 cells as determined by the appearance of matured morphology and the increase in the intracellular hemoglobin level.

Key words

Syzygium levinei - Myrtaceae - alkyl phloroglucinol - cell growth inhibition - differentiation-inducing factor

References

• 1 Hong Kong Herbarium, South China Institute of Botany. Checklist of Hong Kong plants. Hong Kong; Agriculture, Fisheries and Conservation Department Press 2001: p 130
• 2 Srivastava R, Shaw A K, Kulshreshtha D KK. Triterpenoids and chalcone from Syzygium samarangense .  Phytochemistry. 1995;  38 687-9
• 3 Tanaka T, Oriib Y, Nonaka G I, Nishioka I, Kouno I. Syzyginins A and B, two ellagitannins from Syzygium aromaticum .  Phytochemistry. 1996;  43 1345-8
• 4 Charles R, Garg S N, Kumar S. An orsellinic acid glucoside from Syzygium aromatica .  Phytochemistry. 1998;  49 1375-6
• 5 Miyazawa M, Hisama M. Antimutagenic activity of phenylpropanoids from clove (Syzygium aromaticum).  J Agric Food Chem. 2003;  51 6413-22
• 6 Banerjee A, Dasgupta N, De B. In vitro study of antioxidant activity of Syzygium cumini fruit.  Food Chem. 2005;  90 727-33
• 7 Dorit A. Novel anti-viral compounds. WO 9 747 270 1997
• 8 Terreaux C, Maillard M P, Gupta M P, Hostettmann K. Triterpenes and triterpene glycosides from Paradrymonia macrophylla .  Phytochemistry. 1996;  42 495-9
• 9 Houghton P J, Lian L M. Triterpenoids from Desfontainia spinosa .  Phytochemistry. 1986;  25 1939-44
• 10 Zhong X N, Otsuka H, Ide T, Hirata E, Takushi A, Takeda Y. Three flavonol glycosides from leaves of Myrsine seguinii .  Phytochemistry. 1997;  46 943-6
• 11 Fossen T, Larsen Å, Kiremire B T, Andersen O M. Flavonoids from blue flowers of Nymphaea caerulea .  Phytochemistry. 1999;  51 1133-7
• 12 Nonaka G I, Nishimura H, Nishioka I. Tannins and related compounds. IV. Seven phenol glucoside gallates from Quercus stenophylla Makino.  Chem Pharm Bull. 1982;  30 2061-7
• 13 Li B Z, Wang B G, Jia Z J. Pentacyclic triterpenoids from Rubus xanthocarpus .  Phytochemistry. 1998;  49 2477-81
• 14 Saijo R, Nonaka G, Nishioka I. Phenol glucoside gallates from Mallotus japonicus .  Phytochemistry. 1989;  28 2443-6
• 15 Liu X, Zhao D, Wang H. Phenolic compounds from Celastrus angulatus .  J Indian Chem Soc. 2002;  79 259-60
• 16 Zhang C Z, Xu X Z, Li C. Fructosides from Cynomoriun songaricum .  Phytochemistry. 1996;  41 975-6
• 17 Hara S, Okabe H, Mihashi K. Gas-liquid chromatographlic separation of aldose enantiomers as trimethylsilyl ethers of methyl 2-(polyhydroxyalkyl)-thiazolidine-4(R)-carboxylates.  Chem Pharm Bull. 1987;  35 501-6
• 18 Kim S H, Kim T S. Synergistic induction of 1,25-dihydroxyvitamin D₃- and all-trans-retinoic acid-induced differentiation of HL-60 leukemia cells by yomogin, a sesquiterpene lactone from Artemisia princeps .  Planta Med. 2002;  68 886-90
• 19 Tabilio A, Pelicci P G, Vinci G, Mannoni P, Civin C I, Vainchenker W. et al . Myeloid and megakaryocytic properties of K562 cell lines.  Cancer Res. 1983;  43 4569-74
• 20 De Haan J W, Van De Ven L JM. Configurations and conformations in acyclic, unsaturated hydrocarbons. a ¹³C NMR study.  Org Magn Reson. 1973;  5 147-53
• 21 Kaltia S, Matikainen J, Hase T. Z→E Photoisomerization of homoactivated carbon carbon double bonds.  Synth Commun. 1991;  21 1083-6
• 22 Sachs L. The control of hematopoiesis and leukemia: from basic biology to the clinic.  Proc Natl Acad Sci USA. 1996;  93 4742-9
• 23 Masento M S, Morris H R, Taylor G W, Johnson S J, Skapski A C, Kay R R. Differentiation-inducing factor from the slime mould Dictyostelium discoideum and its analogues.  Biochem J. 1988;  256 23-8
• 24 Kubohara Y. Effects of differentiation-inducing factors of Dictyostelium discoideum on human leukemia K562 cells: DIF-3 is the most potent anti-leukemic agent.  Eur J Pharmacol. 1999;  381 57-62

1 These authors contribute equally to this work