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2015 | 62 | 3 | 547-552
Article title

Synthesis of kaempferide Mannich base derivatives and their antiproliferative activity on three human cancer cell lines

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Kaempferide (3,5,7-trihydroxy-4'-methoxyflavone, 1), a naturally occurring flavonoid with potent anticancer activity in a number of human tumour cell lines, was first semisynthesized from naringin. Based on Mannich reaction of kaempferide with various secondary amines and formaldehyde, nine novel kaempferide Mannich base derivatives 2-10 were synthesized. The aminomethylation occurred preferentially in the position at C-6 and C-8 of the A-ring of kaempferide. All the synthetic compounds were tested for antiproliferative activity against three human cancer cell lines (Hela, HCC1954, SK-OV-3) by the standard MTT method. The results showed that compounds 1, 2 and 5-10 were more potent against Hela cells with IC50 values of 12.47-28.24 μM than the positive control cis-platin (IC50 41.25 μM), compounds 5, 6, 8 and 10 were more potent against HCC1954 cells with IC50 values of 8.82-14.97 μM than the positive control cis-platin (IC50 29.68 μM), and compounds 2, 3, 5, 6 and 10 were more potent against SK-OV-3 cells with IC50 values of 7.67-18.50 μM than the positive control cis-platin (IC50 21.27 μM).
Physical description
  • College of Chemistry and Chemical Engineering, Hunan University, Changsha 410082, P R China
  • Faculty of Chemical Engineering, Industry University of Hochiminh City, Vietnam
  • College of Chemistry and Chemical Engineering, Hunan University, Changsha 410082, P R China
  • College of Chemistry and Chemical Engineering, Hunan University, Changsha 410082, P R China
  • College of Chemistry and Chemical Engineering, Hunan University, Changsha 410082, P R China
  • Arend MC, Westermann BH, Risch NL (1998) Modern variants of the Mannich reaction. Angew Chem Int Ed 37: 1044-1070.
  • Arjun H, Yasuhiro T, Jeevan K, Katsumichi M, Ikuo S, Shigetoshi K (1998) Chemical constituents of Brazilian propolis and their cytotoxic activities. J Nat Prod 61: 896-900.
  • Calgarotto AK, Miotto S, Honorio KM, Da ABF, Marangoni S, Silva JL, Comar M Oliverira KMT, Silva SL (2007) A multivariate study on flavonoid compounds scavenging the peroxynitrite free radical. J Mol Struct 808: 25-33.
  • Cao Z, Tong R, Mishra A, Xu W, Wong GC, Cheng J, Lu Y (2009) Reversible cell-specific drug delivery with aptamer-functionalized liposomes. Angew Chem Int Ed Engl 48: 6494-6498.
  • Dharati J, James F, John M, Mohammed A, Heike S, Janet R. Sparrow, George E, Koji N, Arie Z (2013) Synthesis of antioxidants for prevention of age-related macular degeneration. J Nat Prod 76: 450-454.
  • Elbaz AH, Stueckle AT, Wang HL, O'Doherty G, Lowry TD, Sargent ML, Wang L, Dinu CZ, Rojanasakul Y (2012) Digitoxin and a Synthetic monosaccharide analog inhibit cell viability in lung cancer cells. Toxicol Appl Pharmacol 258: 51-60.
  • Gao H, Liu B, Liu F, Chen YS (2010) Anti-proliferative effect of camellianin A in Adinandra nitida leaves and its apoptotic induction in Human Hep G2 and MCF-7 Cells. Molecules 15: 3878-3886.
  • Hattori H, Okuda K, Murase T, Shigetsura Y, Narise K, Semenza GL, Nagasawa H (2011) Isolation, identification, and biological evaluation of HIF-1-modulating compounds from Brazilian green propolis. Bioorg Med Chem 19: 5392-5401.
  • Hattori S, Shimokoriyama M, Kanao M (1952) Studies on flavanone glycosides. IV. The glycosides of ripe fruit peel and flower petals of citrus aurantium L. J Amer Chem Soc 74: 3614-3615.
  • Hiroko T, Keiko H, Tomoki T, Ken H, Hiroyuki K, Shunya T (2010) Inhibitory activity of Brazilian green propolis components and their derivatives on the release of cys-leukotrienes. Bioorg Med Chem 18: 151-157.
  • Liu D, Qu W, Liang JY (2013) Flavonoids and other constituents from Alpinia sichuanensis Z.Y. Zhu. Biochem Systematics and Ecology 46: 127-129.
  • Liu JD, Chen L, Cai SL, Wang QA (2012) Semisynthesis of apigenin and acacetin-7-O-β-d-glycosides from naringin and their cytotoxic activities. Carbohydr Res 357: 41-46.
  • Liu RH, Huang XQ, Lou DH, Liu XJ, Liu WK, Wang QA (2014) Synthesis and acetylcholinesterase inhibitory activity of Mannich base derivatives flavokawain B Bio Med Chem Lett 24: 4749-4753.
  • Martineti V, Tognarini I, Azzari C, Carbonell S, Clematis F, Dolci M, Lanzotti V, Tonelli F, Brandi ML, Curir P (2010) Inhibition of in vitro growth and arrest in the G0/G1 phase of HCT8 line human colon cancer cells by kaempferide triglycoside from Dianthus caryophyllus. Phytother Res 24: 1302-1308.
  • Matsuda H, Nakashima S, Oda Y, Nakamura S, Yoshikawa M (2009) Melanogenesis inhibitors from the rhizomes of alpinia officinarum in B16 melanoma cells. Bio Med Chem 17: 6048-6053.
  • Omayma A, Eldahshan (2013) Rhoifolin; A potent antiproliferative effect on cancer cell lines. British J Pharm Res 3: 45-53.
  • Sharma RC, Zaman A, Kidwai AR (1963) Chemical examination of Buddleia asiatica. Indian J Chem 1(8): 366-367.
  • Sujith KV, Rao JN, Shetty P, Kalluraya B (2009) Regioselective reaction: synthesis and pharmacological study of Mannich bases containing ibuprofen moiety. Eur J Med Chem 44: 3697-3702.
  • Tasdemir D, Kaiser M, Brun R, Yardley V, Schmidt T, Tosun F, Rüedi P (2006) Antitrypanosomal and antileishmanial activities of flavonoids and their analogues: in vitro, in vivo, structure-activity relationship, and quantitative structure-activity relationship studies. Antimicrob Agents Chemother 50: 1352-1364.
  • Wu Z, Nguyen VS, Liu ZK, Wang QA (2013) A Facile 'Click Chemistry' Approach to Novel Flavonol Glycoconjugates and Their Cytotoxic Activity. Lett Org Chem 10: 674-682.
  • Xu SH, Liu HR, Lou DH, Wang QA (2014) Synthesis and AChE inhibitory activity of chalcones Mannich base derivatives. Chin J Org Chem 34: 749-755.
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