- Synthesis of new N1-substituted-5-aryl-3-(3,4,5-trimethoxyphenyl)-2-pyrazoline derivatives as antitumor agents targeting the colchicine site on tubulin
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A series of pyrazoline derivatives 2a-e, 3a-e and 4a-e structurally related to combretastatin A4 (CA-4) were synthesized and characterized by spectroscopic means and elemental analyses. In these compounds, the cis double bond of CA-4 was replaced with the pyrazoline ring aiming to enhance the cytotoxic effects displayed by CA-4 and to prevent the cis/trans isomerization that is associated with inactivation of CA-4. The cytotoxic activity of all new compounds was investigated in vitro against MCF-7 and HCT-116 cell lines. The inhibition of tubulin polymerization by the most active compounds 3d, 4a and e was evaluated. The cytotoxicity of 4e was correlated with induction of apoptosis and caspase-3 activation in vitro thus indicating the apoptotic pathway of anticancer effect of these compounds. Furthermore, in vivo evaluation of the synthesized compounds was carried out against Ehrlich's ascites carcinoma (EAC) solid tumor grown in mice. Compounds 2c, 3a and e showed significant reduction in tumor weight, and about 2-4 fold increase in caspase-3 expression.
- Elmeligie, Salwa,Khalil, Nadia Abdalla,Ahmed, Eman Mohamed,Emam, Soha Hussein,Zaitone, Sawsan Abo-Bakr
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- A novel series of benzothiazepine derivatives as tubulin polymerization inhibitors with anti-tumor potency
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In this work, a series of diaryl benzo[b][1,4]thiazepine derivatives D1-D36 were synthesized and screened as tubulin polymerization inhibitors with anti-tumor potency. They were designed by introducing the seven-member ring benzothiazepine as the linker f
- Wang, Bin,Wang, Li-Ren,Liu, Lu-Lu,Wang, Wei,Man, Ruo-Jun,Zheng, Da-Jun,Deng, Yu-Shan,Yang, Yu-Shun,Xu, Chen,Zhu, Hai-Liang
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- The synthesis of chalcones as anticancer prodrugs and their bioactivation in CYP1 expressing breast cancer cells
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Background: Although the expression levels of many P450s differ between tumour and corresponding normal tissue, CYP1B1 is one of the few CYP subfamilies which is significantly and consistently overexpressed in tumours. CYP1B1 has been shown to be active within tumours and is capable of metabolising a structurally diverse range of anticancer drugs. Because of this, and its role in the activation of procarcinogens, CYP1B1 is seen as an important target for anticancer drug development. Objective: To synthesise a series of chalcone derivatives based on the chemopreventative agent DMU-135 and investigate their antiproliferative activities in human breast cancer cell lines which express CYP1B1 and CYP1A1. Method: A series of chalcones were synthesised in yields of 43-94% using the Claisen-Schmidt condensation reaction. These were screened using a MTT assay against a panel of breast cancer cell lines which have been characterised for CYP1 expression. Result: A number of derivatives showed promising antiproliferative activities in human breast cancer cell lines which express CYP1B1 and CYP1A1, while showing significantly lower toxicity towards a non-tumour breast cell line with no CYP expression. Experiments using the CYP1 inhibitors acacetin and α-naphthoflavone provided supporting evidence for the involvement of CYP1 enzymes in the bioactivation of these compounds. Conclusion: Chalcones show promise as anticancer agents with evidence suggesting that CYP1 activation of these compounds may be involved.
- Ruparelia, Ketan C.,Zeka, Keti,Ijaz, Taeeba,Ankrett, Dyan N.,Wilsher, Nicola E.,Butler, Paul C.,Tan, Hoon L.,Lodhi, Sabahat,Bhambra, Avninder S.,Potter, Gerard A.,Arroo, Randolph R.J.,Beresford, Kenneth J.M.
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p. 322 - 332
(2018/06/26)
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- Identification of 3',4',5'-trimethoxychalcone analogues as potent inhibitors of Helicobacter pylori-induced inflammation in human gastric epithelial cells
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Efforts to identify potent small molecule inhibitors of Helicobacter pylori led to the evaluation of 23 3',4',5'-trimethoxychalcone analogues. Some of the compounds displayed potent antibacterial activity against H. pylori. Three most active and selective
- Lai, Chih-Ho,Rao, Yerra Koteswara,Fang, Shih-Hua,Sing, Yu-Ting,Tzeng, Yew-Min
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supporting information; experimental part
p. 5462 - 5465
(2011/01/03)
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- Combretastatin-like chalcones as inhibitors of microtubule polymerization. Part 1: Synthesis and biological evaluation of antivascular activity
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The α-methyl chalcone SD400 is a potent inhibitor of tubulin assembly and possesses potent anticancer activity. Various chalcone analogues were synthesized and evaluated for their cell growth inhibitory properties against the K562 human chronic myelogenous leukemia cell line (SD400, IC50 0.21 nM; combretastatin A4 CA4, IC50 2.0 nM). Cell cycle analysis by flow cytometry indicated that these agents are antimitotic (SD400, 83% of the cells are in G2/M phase; CA4 90%). They inhibit tubulin assembly at low concentration (SD400, IC50 0.46 μM; CA4, 0.10 μM) and compete with [3H]colchicine for binding to tubulin (8% [3H]colchicine remained bound to tubulin after competition with SD400 or CA4). Upon treatment with SD400, remarkable cell shape changes were elicited in HUVEC cells, consistent with vasculature damaging activity.
- Ducki, Sylvie,Rennison, David,Woo, Meiko,Kendall, Alexander,Chabert, Jeremie Fournier Dit,McGown, Alan T.,Lawrence, Nicholas J.
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supporting information; experimental part
p. 7698 - 7710
(2010/03/24)
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- Synthesis and biological evaluation of 3′,4′,5′-trimethoxychalcone analogues as inhibitors of nitric oxide production and tumor cell proliferation
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A series of 23 3′,4′,5′-trimethoxychalcone analogues was synthesized and their inhibitory effects on nitric oxide (NO) production in LPS/IFN-γ-treated macrophages, and tumor cell proliferation has been investigated. 4-Hydroxy-3,3′,4′,5′-tetramethoxychalco
- Rao, Yerra Koteswara,Fang, Shih-Hua,Tzeng, Yew-Min
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experimental part
p. 7909 - 7914
(2010/03/25)
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- Design, synthesis, and biological evaluation of thiophene analogues of chalcones
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Chalcones are characterized by possessing an enone moiety between two aromatic rings. A series of chalcone-like agents, in which the double bond of the enone system is embedded within a thiophene ring, were synthesized and evaluated for antiproliferative
- Romagnoli, Romeo,Baraldi, Pier Giovanni,Carrion, Maria Dora,Cara, Carlota Lopez,Cruz-Lopez, Olga,Preti, Delia,Tolomeo, Manlio,Grimaudo, Stefania,Cristina, Antonella Di,Zonta, Nicola,Balzarini, Jan,Brancale, Andrea,Sarkar, Taradas,Hamel, Ernest
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p. 5367 - 5376
(2008/12/20)
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- Synthesis and biological evaluation of chalcones and their derived pyrazoles as potential cytotoxic agents
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A series of substituted chalcones and their corresponding pyrazoles were synthesized and evaluated for in vitro cytotoxic activity against a panel of human cancer cell lines. Out of 93 compounds screened, 8 compounds, 1s, 3i,j,n, 4i,j,n and 4s, showed marked activity. Compounds 4j,n and 4s were found to be the most promising in this study. SAR is also discussed.
- Bhat,Dhar,Puri,Saxena,Shanmugavel,Qazi
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p. 3177 - 3180
(2007/10/03)
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