Tao Gan, Yang Cheng, Wenhao Tian, Zhiping Liu, Chunfang Gan, Yanmin Huang, Chunrui Cai, Jianguo Cui
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引用次数: 0
Abstract
Cancer is one of the most significant diseases that afflict human beings. The pursuit of high efficacy and low-toxicity anticancer drugs has always been a paramount research objective for scientists. In the present study, we incorporated two selenocyano pharmacophores into the 2-site and 17-branch chain of the steroid nucleus in various manners, utilizing estradiol as the fundamental framework. Consequently, several estradiol bisselenocyanate compounds with a 2-selenocyano-17-selenocyanoester structure were synthesized. When compared to the positive control steroidal anti-tumor drug 2-methoxyestradiol, certain derivatives exhibited superior inhibitory activity against tumor cells in vitro, surpassing their monoselenocyanate precursors. The representative compound 4b induced programmed apoptosis in HeLa cells in a concentration-dependent manner during apoptosis and cell cycle experiments, while causing G2 phase arrest predominantly in the cell cycle. Moreover, compound 4b exhibited significant inhibitory effects on cell migration and demonstrated remarkable inhibitory activity against HeLa xenograft tumors in zebrafish models. These findings suggest that these compounds hold potential as promising candidates for anti-tumor drugs and warrant further investigation.
期刊介绍:
Molecular Diversity is a new publication forum for the rapid publication of refereed papers dedicated to describing the development, application and theory of molecular diversity and combinatorial chemistry in basic and applied research and drug discovery. The journal publishes both short and full papers, perspectives, news and reviews dealing with all aspects of the generation of molecular diversity, application of diversity for screening against alternative targets of all types (biological, biophysical, technological), analysis of results obtained and their application in various scientific disciplines/approaches including:
combinatorial chemistry and parallel synthesis;
small molecule libraries;
microwave synthesis;
flow synthesis;
fluorous synthesis;
diversity oriented synthesis (DOS);
nanoreactors;
click chemistry;
multiplex technologies;
fragment- and ligand-based design;
structure/function/SAR;
computational chemistry and molecular design;
chemoinformatics;
screening techniques and screening interfaces;
analytical and purification methods;
robotics, automation and miniaturization;
targeted libraries;
display libraries;
peptides and peptoids;
proteins;
oligonucleotides;
carbohydrates;
natural diversity;
new methods of library formulation and deconvolution;
directed evolution, origin of life and recombination;
search techniques, landscapes, random chemistry and more;