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A Focused Library of NO‐Donor Compounds with Potent Antiproliferative Activity Based on Green Multicomponent Reactions
Author(s) -
Ingold Mariana,
Colella Lucía,
Hernández Paola,
Batthyány Carlos,
Tejedor David,
Puerta Adrián,
GarcíaTellado Fernando,
Padrón José M.,
Porcal Williams,
López Gloria. V.
Publication year - 2019
Publication title -
chemmedchem
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.817
H-Index - 100
eISSN - 1860-7187
pISSN - 1860-7179
DOI - 10.1002/cmdc.201900385
Subject(s) - chemistry , stereochemistry , cytotoxicity , structure–activity relationship , nitric oxide , cell culture , lead compound , combinatorial chemistry , biological activity , biochemistry , in vitro , biology , organic chemistry , genetics
Abstract Cancer is the second leading cause of death worldwide. Herein, a strategy to quickly and efficiently identify novel lead compounds to develop anticancer agents, using green multicomponent reactions followed by antiproliferative activity and structure–activity relationship studies, is described. A second‐generation focused library of nitric oxide‐releasing compounds was prepared by microwave‐assisted Passerini and Ugi reactions. Nearly all compounds displayed potent antiproliferative activities against a panel of human solid tumor cell lines, with 1‐phenyl‐1‐[( tert ‐butylamino)carbonyl]methyl 3‐[(3‐phenylsulfonyl‐[1,2,5]oxadiazol‐4‐yl N 2 ‐oxide)oxy]benzoate ( 4 k ) and N ‐[1‐( tert ‐butylaminocarbonyl)‐1‐phenylmethyl]‐ N ‐(4‐methylphenyl)‐3‐(3‐phenylsulfonyl‐[1,2,5]oxadiazol‐4‐yl N 2 ‐oxide)oxyphenyl carboxamide ( 6 d ) exhibiting the strongest activity on SW1573 lung cell line (GI 50 =110 and 21 n m ) with selectivity indices of 70 and 470, respectively. Preliminary mechanistic studies suggest a relationship between NO release and antiproliferative activity. Our strategy allowed the rapid identification of at least two molecules as future candidates for the development of potent antitumor drugs.