Novel quinazoline and pyrido[2,3-d]pyrimidine derivatives and their hydroselenite salts as antitumoral agents

Abstract

Dedicated to Rosa M. Claramunt Vallespí on the occasion of her 65th anniversary Abstract A series of 22 quinazolines, pyrido [2,3-d]pyrimidines and their hydroselenite salts were synthesized with the aim of evaluating in vitro their cytotoxicity against PC-3 cell line and their antioxidant properties related to DPPH (1,1-diphenyl-2-picrylhydrazylradical) activity, showing some of them better profile than the respective controls. Three of these derivatives (5d, 6d and 7f) were selected in order to gain preliminary insights to establish the mechanism of action. Caspase-3 activity and cell cycle regulation studies revealed that compound 6d provoked an increase in caspase-3 level accompanied by cell cycle perturbation in a time-dependent manner.

Recent advances in the chemistry and biology of pyridopyrimidines

“…Alkylation of the selenium atom with various alkyl iodides was performed to give library 125 (Scheme 37).Compound 127 exhibited a marked cytotoxic effect on leukemia CCFF-CEM, colon HT-29, lung HTB-54, breast MCF-7 cell lines and replacement of the sulfur by a selenium atom 126 did not significantly affect biological activity[41]. An increase in Caspase-3 activity accompanied by cell cycle perturbation in a time-dependent manner was demonstrated with the hydroselenite salt 128 (Scheme 38)[42].Malhotra et al investigated the synthesis of 4-substituted 2-amino pyrido[3,4-d]pyrimidine derivatives 129 as potential anticancer agents. A tumor cell line screening was performed using the NCI 60 cancer cell lines panel, and showed inhibitory effects against the growth of the UO-31 renal cancer cell line, MDA-MB-468 and MCF-7 breast cancer cell lines (Scheme 39)[17].…”