EFFECTS OF TWO NEW SYNTHESIZED HETEROCYCLIC COMPOUNDS ON PROLIFERATION AND TUBE FORMATION OF ENDOTHELIAL CELLS AND ON ANGIOGENESIS IN CHICKEN CHORIOALLANTOIC MEMBRANE

摘要

Angiogenesis is a central process in the growth of solid tumors. In the present work, the anti-angiogenic effects of two new synthesized pyrimidine cyano sulfanyl and tetraazolo thiadiazepino quinoline derivatives (namely PCS and TZQ, respectively) were investigated in NIH/3T3 fibroblasts and human umbilical vein endothelial cells (HUVECs) in vitro and in chicken chorioallantoic membrane (CAM) ex vivo . Cytotoxicity of the compounds was measured in HUVECs and NIH/3T3 cells using thiazolyl blue tetrazolium bromide (MTT) assay. Effects of the compounds on vessel-like tube formation by HUVECs were examined in Matrigel-based assay. Also, CAM was used as a model of angiogenesis to evaluate anti-angiogenic effect of the compounds in vivo . PCS led to a significant reduction of the viability of NIH/3T3 cells and HUVECs with IC50 values of 37.91 mu M and 64.77 mu M, respectively. The TZQ was found to be more potent than PCS with IC50 values of 8.6 mu M and 43.65 mu M for NIH/3T3 cells and HUVECs, respectively. Moreover, PCS at concentrations = 500 mu M significantly reduced formation of neovessels in CAM. The inhibitory effect of TZQ on neovascular formation was started from concentration of 100 mu M. Besides, the effects of PCS and TZQ on tube formation in HUVECs was started from concentrations of 20 and 10 mu M, respectively. In conclusion, this study demonstrated that the synthesized heterocyclic compounds have anti-angiogenic effects and, therefore, can be subjected to further studies as anti-tumor agents.