A modular approach to trim cellular targets in anticancer drug discovery

• Published in: Bioorganic & medicinal chemistry letters Vol. 21; no. 22; pp. 6641 - 6645
• Main Authors: Ríos-Luci, Carla, Domínguez-Kelly, Raquel, León, Leticia G., Díaz-Rodríguez, Elena, Freire, Raimundo, Pandiella, Atanasio, Cikotiene, Inga, Padrón, José M.
• Format: Journal Article
• Language: English
• Published: Amsterdam Elsevier Ltd 15.11.2011; Elsevier
• Subjects: Anaphase - drug effects; Antineoplastic Agents - chemical synthesis; Antineoplastic Agents - chemistry; Antineoplastic Agents - pharmacology; Antitumor agents; Biological and medical sciences; Cell cycle; Cell Cycle - drug effects; Cell Line, Tumor; Drug Discovery; Humans; Medical sciences; Metaphase - drug effects; Mitotic arrest; Neoplasms - drug therapy; Oxidation-Reduction; Pharmacology. Drug treatments; Phenotypic Drug Discovery; Pyrimidines - chemical synthesis; Pyrimidines - chemistry; Pyrimidines - pharmacology; Structure-Activity Relationship; Structure–activity relationships; Antitumor agents; Mitotic arrest; Phenotypic Drug Discovery; Structure–activity relationships; Cell cycle; Antineoplastic agent; Structure activity relation; Targeted drug; Structure-activity relationships; In vitro; Research and development
• ISSN: 0960-894X; 1464-3405
• DOI: 10.1016/j.bmcl.2011.09.069

A Phenotypic Drug Discovery strategy was applied to study a set of pyrimidine analogs prepared by means of intramolecular oxidation–reduction reactions of N-substituted- N-(2,6-disubstituted-5-nitro-4-pyrimidinyl)aminoacetic acid methyl esters in basic media. The combined and rational use of specific assays allowed in short time reducing from all possible cellular targets to those involved in metaphase to anaphase transition.