Medicinal Chemistry Research

, Volume 26, Issue 10, pp 2692–2698 | Cite as

Synthesis and antiproliferative properties of novel naringenin derivatives

Original Research

Abstract

In order to improve the antiproliferative activity of naringenin, a naturally occurred flavonoid in citrus fruits, a series of naringenin derivatives with a tertiary amino side chain were prepared. The antiproliferative activities of these naringenin derivatives were evaluated on four human cancer cell lines, namely, MCF-7, HCT116, Hela, and A549. Compounds 4a, 9a, and 10a exhibited remarkably enhanced growth inhibition activity. Based on the observed results, the structure–activity relationship of these derivatives was discussed.

Keywords

Naringenin Antiproliferative activity Synthesis Derivatives 

Notes

Acknowledgements

This work was partially supported by the grants from the National Natural Science Foundation of China (No. 20672147, No. 21472247).

Compliance with ethical standards

Conflict of interest

The authors declare that they have no competing interests.

References

  1. Arul D, Subramanian P (2013) Naringenin (citrus flavonone) induces growth inhibition, cell cycle arrest and apoptosis in human hepatocellular carcinoma cells. Pathol Oncol Res 19:763–770CrossRefPubMedGoogle Scholar
  2. Bak Y, Kim H, Kang J-W, Lee DH, Kim MS, Park YS, Kim J-H, Jung K-Y, Lim Y, Hong J, Yoon D-Y (2011) A synthetic naringenin derivative, 5-Hydroxy-7,4′-diacetyloxyflavanone-N-phenyl Hydrazone (N101-43), induces apoptosis through up-regulation of Fas/FasL expression and inhibition of PI3K/Akt signaling pathways in non-small-cell lung cancer cells. J Agric Food Chem 59:10286–10297CrossRefPubMedGoogle Scholar
  3. Benavente-Garcia O, Castillo J, Marin FR, Ortuno A, Del Rio JA (1997) Uses and properties of citrus flavonoids. J Agric Food Chem 45:4505–4515CrossRefGoogle Scholar
  4. Chen J-W, Zhu Z-Q, Hu T-X, Zhu D-Y (2002) Structure-activity relationship of natural flavonoids in hydroxyl radical-scavenging effects. Acta Pharmacol Sin 23:667–672PubMedGoogle Scholar
  5. Felgines C, Texier O, Morand C, Manach C, Scalbert A, Regerat F, Remesy C (2000) Bioavailability of the flavanone naringenin and its glycosides in rats. Am J Physiol Gastrointest Liver Physiol 279:G1148–G1154PubMedGoogle Scholar
  6. Fuhr U, Klittich K, Staib AH (1993) Inhibitory effect of grapefruit juice and its bitter principal, naringenin, on CYP1A2 dependent metabolism of caffeine in man. Br J Clin Pharmacol 35:431–436CrossRefPubMedPubMedCentralGoogle Scholar
  7. Heo HJ, Kim DO, Shin SC, Kim MJ, Kim BJ, SHIN DH (2004) Effect of antioxidant flavanone, naringenin, from citrus junos on neuroprotection. J Agric Food Chem 52:1520–1525CrossRefPubMedGoogle Scholar
  8. Kanno S, Tomizawa A, Hiura T, Osanai Y, Shouji A, Ujibe M, Ohtake T, Kimura K, Ishikawa M (2005) Inhibitory effects of naringenin on tumor growth in human cancer cell lines and sarcoma S-180-implanted mice. Biol Pharm Bull 28:527–530CrossRefPubMedGoogle Scholar
  9. Kawaii S, Tomono Y, Katase E, Ogawa K, Yano M (1999) HL-60 differentiating activity and flavonoid content of the readily extractable fraction prepared from citrus juices. J Agric Food Chem 47:128–135CrossRefPubMedGoogle Scholar
  10. Kim H, Lee E, Kim J, Kim J, Lim H, Lee C-H, Ahn J-H, Chong Y, Lim Y (2007) Binding study of naringenin derivatives and cyclin dependent kinase 2. Bull Korean Chem Soc 28:1413–1415CrossRefGoogle Scholar
  11. Lee E-R, Kang Y-J, Choi H-Y, Kang G-H, Kim J-H, Kim B-W, Han YS, Nan S-Y, Paik H-D, Park Y-S, Cho S-G (2007) Induction of apoptotic cell death by synthetic naringenin derivatives in human lung epithelial carcinoma A549 cells. Biol Pharm Bull 30:2394–2398CrossRefPubMedGoogle Scholar
  12. Lee SH, Park YB, Bae KH, Bok SH, Kwon YK, Lee ES, Choi MS (1999) Cholesterol-lowering activity of naringenin via inhibition of 3-hydroxy-3-methylglutaryl coenzyme A reductase and acyl coenzyme A: cholesterol acyltransferase in rats. Ann Nutr Metab 43:173–180CrossRefPubMedGoogle Scholar
  13. Liu Z, Wei W, Gan C, Huang Y, Liu S, Zhou M, Cui J (2013) Semisynthesis and cytotoxicity of E-naringenin oximes from naringin. Chin J Org Chem 33:2551–2558CrossRefGoogle Scholar
  14. Moon YJ, Wang X, Morris ME (2006) Dietary flavonoids: Effects on xenobiotic and carcinogen metabolism. Toxicol in Vitro 20:187–210CrossRefPubMedGoogle Scholar
  15. Park JH, Jin CY, Lee BK, Kim GY, Choi YH, Jeong YK (2008) Naringenin induces apoptosis through downregulation of Akt and caspase-3 activation in human leukemia THP-1 cells. Food Chem Toxicol 46:3684–3690CrossRefPubMedGoogle Scholar
  16. Sabarinathan D, Mahalakshmi P, Vanisree AJ (2010) Naringenin promote apoptosis in cerebrally implanted C6 glioma cells. Mol Cell Biochem 345:215–222CrossRefPubMedGoogle Scholar
  17. Sabarinathan D, Vanisree AJ (2013) Plausible role of naringenin against cerebrally implanted C6 glioma cells in rats. Mol Cell Biochem 375:171–178PubMedGoogle Scholar
  18. Semalty A, Semalty M, Singh D, Rawat MSM (2010) Preparation and characterization of pospholipid complexes of naringenin for effective drug delivery. J Incl Phenom Macrocycl Chem 67:253–260CrossRefGoogle Scholar
  19. Yoon H, Kim TW, Shin SY, Park MJ, Yong Y, Kim DW, Islam T, Lee YH, Jung K-Y, Lim Y (2013) Design, synthesis and inhibitory activities of naringenin derivatives on human colon cancer cells. Bioorg Med Chem Lett 23:232–238CrossRefPubMedGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2017

Authors and Affiliations

  1. 1.School of Pharmaceutical SciencesCentral South UniversityChangshaChina
  2. 2.School of Life SciencesCentral South UniversityChangshaChina

Personalised recommendations