In search of new anticancer drug - Dimethylsulfoxide ruthenium(III) complex with bulky triazolopyrimidine derivative and preliminary studies towards understanding the mode of action

摘要

By reacting of [H(dmso)(2)]trans-[RuCl4(dmso)(2)] with 5,7-ditertbutyl-1,2,4-triazolo[1,5-a]pyrimidine (dbtp) in molar ratio of M:L = 1:2 new ruthenium(III) complex mer,cis-[RuCl3(dbtp)(2)(dmso)] has been prepared and structurally characterized by X-ray, IR and EPR spectroscopies. The crystal structure of the Ru(III) complex showed slightly distorted octahedral geometry with unique cis positioned monodentate dbtp ligands bound to the ruthenium(III) ion through the N3 nitrogen atom. In vitro toxicity assay proves that slightly lipophilic the mer,cis-[RuCl3(dbtp)(2)(dmso)] (logP = 0.80) is 5-fold less toxic against non-tumorigenic human epithelial cell line (MCF-10A) and normal murine embryonic fibroblast cells (BALB/3T3) than cisplatin. Preliminary studies towards understanding the mode of action suggested that activation by reduction, electrostatic interactions of the mer,cis-[RuCl3(dbtp)(2)(dmso)] With CT-DNA and selective delivery to cells by apotransferrin might be relevant for the biological properties of the complex. (C) 2017 Elsevier Ltd. All rights reserved.