Biological activity screening of DL0805 derivatives and the cytotoxicity evaluation
Abstract：Objective:To evaluate the in vitro activity of 105 derivatives of DL0805,a Rho-kinase inhibitor with indazole scaffold discovered in our previous work,and discover potential candidate compounds.Methods:Rho-kinase inhibitors among these 105 compounds were screened by ELISA and the vasorelaxant effects of these compounds on isolated rat thoracic aorta rings were evaluated.The toxicity tests were performed on two kinds of vascular cells including VSMC (vascular smooth muscle cells) and HUVEC (human umbilical vein endothelial cells).Also the inhibitory effects on VSMC proliferation were tested by MTT assay.Results:After preliminary and secondary screening,it was found that there were five compounds owning potent Rho-kinase inhibitory effect.Twenty-two compounds had vasodilatory effect on isolated aorta rings.Only one compound exhibited toxicity on VSMC and five compounds could inhibit the proliferation of VSMC induced by FBS.Meanwhile,three compounds were toxic on HUVEC.Conclusion:There are five compounds from the 105 DL0805 derivatives having the potential for further development.Among them,four compounds are new chemical entities,which deserve more investigation.
Keywords：DL0805 derivativesRho kinaseisolated aorta ringsvascular smooth muscle cellshuman umbilical vein endothelial cells
Publication Date：2016-01-01
Online Publishing Date：2026-08-14(First online date of this platform, not the publication date of the document)