Anti‐Tumor Activity of New Artemisinin–Chalcone Hybrids

In an attempt to develop potent and selective anti‐tumor agents, three new series of artemisinin–chalcone hybrids 10a–10g, 11a–11g and 12a–12h were designed, synthesized and screened for their anti‐tumor activity against five cell lines (HT‐29, A549, MDA‐MB‐231, HeLa and H460) in vitro. Among compounds 10a–g and 11a–11g, most of them displayed enhanced activity and good selectivity toward HT‐29 and HeLa cell lines with IC50 values ranging from 0.12 to 0.85 µM as compared with DHA (dihydroartemisinin). Compounds 10a and 11a are most active toward HeLa cells with IC50 values of 0.12 and 0.19 µM. The results revealed that the presence of chalcone moiety is beneficial to their activity and selectivity. In addition, compounds 12a‐12h containing a ‘reversed chalcone’ moiety showed only slight improvement in activity than those of DHA.

[1]  X. Zhai,et al.  (1R,3S,4R,4aS,7R,7aS,10R,12aR)-3-Azido-4,7,10-trimethyl-1,10-epidioxyperhydropyrano[4,3-j][1,2]benzodioxepine , 2010, Acta crystallographica. Section E, Structure reports online.

[2]  Junjie Tan,et al.  Synthesis of a series of novel dihydroartemisinin derivatives containing a substituted chalcone with greater cytotoxic effects in leukemia cells. , 2009, Bioorganic & medicinal chemistry letters.

[3]  Jun O. Liu,et al.  Malaria-infected mice are cured by a single oral dose of new dimeric trioxane sulfones which are also selectively and powerfully cytotoxic to cancer cells. , 2009, Journal of medicinal chemistry.

[4]  Gurmeet Kaur,et al.  Synthesis and evaluation of dihydroartemisinin and dihydroartemisitene acetal dimers showing anticancer and antiprotozoal activity. , 2009, Bioorganic & medicinal chemistry.

[5]  J. Ham,et al.  Synthesis of 10-substituted triazolyl artemisinins possessing anticancer activity via Huisgen 1,3-dipolar cylcoaddition. , 2009, Bioorganic & medicinal chemistry letters.

[6]  Woong Nam,et al.  Effects of artemisinin and its derivatives on growth inhibition and apoptosis of oral cancer cells , 2007, Head & neck.

[7]  G. Cohen,et al.  Evidence for the Involvement of Carbon-centered Radicals in the Induction of Apoptotic Cell Death by Artemisinin Compounds* , 2007, Journal of Biological Chemistry.

[8]  Y. Hsu,et al.  Chalcone inhibits the proliferation of human breast cancer cell by blocking cell cycle progression and inducing apoptosis. , 2006, Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association.

[9]  Kwang-Kyun Park,et al.  Antiangiogenic activity of deoxoartemisinin derivatives on chorioallantoic membrane. , 2006, Bioorganic & medicinal chemistry letters.

[10]  T. Efferth.  Mechanistic perspectives for 1,2,4-trioxanes in anti-cancer therapy. , 2005, Drug resistance updates : reviews and commentaries in antimicrobial and anticancer chemotherapy.

[11]  X. Wu,et al.  Chalcones: an update on cytotoxic and chemoprotective properties. , 2005, Current medicinal chemistry.

[12]  F. Oesch,et al.  Enhancement of cytotoxicity of artemisinins toward cancer cells by ferrous iron. , 2004, Free radical biology & medicine.

[13]  W. Shin,et al.  Synthesis and antiangiogenic activity of thioacetal artemisinin derivatives. , 2004, Bioorganic & medicinal chemistry.

[14]  Y. Tzeng,et al.  Differential effects of synthesized 2'-oxygenated chalcone derivatives: modulation of human cell cycle phase distribution. , 2004, Bioorganic & medicinal chemistry.

[15]  J. Vaya,et al.  Chalcones as potent tyrosinase inhibitors: the effect of hydroxyl positions and numbers. , 2004, Phytochemistry.

[16]  Hui-jun Zhou,et al.  Inhibitory Effects of Artesunate on Angiogenesis and on Expressions of Vascular Endothelial Growth Factor and VEGF Receptor KDR/flk-1 , 2004, Pharmacology.

[17]  I. Mellinghoff,et al.  The emergence of resistance to targeted cancer therapeutics. , 2002, Pharmacogenomics.

[18]  S. Kane,et al.  Transferrin overcomes drug resistance to artemisinin in human small-cell lung carcinoma cells. , 2002, Cancer letters.

[19]  N. Singh,et al.  Selective toxicity of dihydroartemisinin and holotransferrin toward human breast cancer cells. , 2001, Life sciences.

[20]  M. Narasu,et al.  Current status of artemisinin and its derivatives as antimalarial drugs. , 1999, Life sciences.

[21]  T. Shapiro,et al.  Antimalarial, antiproliferative, and antitumor activities of artemisinin-derived, chemically robust, trioxane dimers. , 1999, Journal of medicinal chemistry.

[22]  M. Alcaraz,et al.  Synthesis and anti-inflammatory activity of chalcone derivatives. , 1998, Bioorganic & medicinal chemistry letters.

[23]  N. Lawrence,et al.  Potent antimitotic and cell growth inhibitory properties of substituted chalcones. , 1998, Bioorganic & medicinal chemistry letters.

[24]  M. Wani,et al.  Camptothecin and taxol: discovery to clinic--thirteenth Bruce F. Cain Memorial Award Lecture. , 1995, Cancer research.

[25]  M. Iinuma,et al.  Anti-Candida activity of synthetic hydroxychalcones. , 1994, Die Pharmazie.

[26]  M. L. Edwards,et al.  Chalcones: a new class of antimitotic agents. , 1990, Journal of medicinal chemistry.