Synthesis of Novel 1,3,4-Trisubstituted Pyrazole Derivatives and Their Evaluation as Antitumor and Antiangiogenic Agents

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概要

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• Several 1,3,4-trisubstituted pyrazole derivatives were synthesized and screened for their cytotoxic effect in a primary 3 tumor cell line test at 10_<-4>M drug concentration. Compounds 19 and 20 reduced the growth of one or more of these cell lines to less than 32% and escalated up to evaluation in the full panel of 60 human tumor cell lines at a minimum of 5 concentrations at 10 fold dilutions. Compound N'-(1-{1-[4-nitrophenyI]-3-phenyl-1H-pyrazol-4-yl}methylene)-2-chlorobenzohydrazide 19 proved to be the most active of these derivatives with full panel median growth inhibition (GI_<50>), total growth concentration (TGI) and median lethal concentration (LC_<50>) mean graph mid-point (MG-M1D) of 3.79, 12.5 and 51.5μM, respectively. In addition, compounds 19, 39, 40, 41, 43, 45, 47 were tested for their antiangiogenic properties by testing their ability to inhibit human umbilical vein endothelial cells (HUVECs) proliferation, cord formation and migration in response to chemoattractant. 3-Acety1-2-(1-(4-nitrophenyl)-3-phenylpyrazol-4-yl)-5-(4-pyridyl)-l,3,4-oxadiazoline 39 showed significant antiangiogenic profile at non-cytotoxic doses, with HUVEC proliferation inhibition IC_<50> of 7.60 μM, chemotaxis IC_<50> of 0.86 μM and was superior to the reference celecoxib 2 in both tests. Furthermore, in contrary to the references TNP-470 and celecoxib, all the tested compounds interfered with the migratory function of HUVECs in response to vascular endothelium growth factor (VEGF) rather than the endothelial cells proliferation.

• 2003-07-01

著者

• Eissa Amal

  Department Of Pharmaceutical Chemistry Faculty Of Pharmacy Cairo University

• ABADI Ashraf

  Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Cairo University

• HASSAN Ghaneya

  Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Cairo University

• Abadi Ashraf

  Department Of Pharmaceutical Chemistry Faculty Of Pharmacy Cairo University

• Hassan Ghaneya

  Department Of Pharmaceutical Chemistry Faculty Of Pharmacy Cairo University

関連論文

• Synthesis and Anticonvulsant Activity of Certain Substituted Furochromone, Benzofuran and Flavone Derivatives
• Synthesis of Novel 1,3,4-Trisubstituted Pyrazole Derivatives and Their Evaluation as Antitumor and Antiangiogenic Agents
• Modulating the Cyclic Guanosine Monophosphate Substrate Selectivity of the Phosphodiesterase 3 Inhibitors by Pyridine, Pyrido[2,3-d]pyrimidine Derivatives and Their Effects upon the Growth of HT-29 Cancer Cell Line

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