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N ‐(Indazolyl)benzamido Derivatives as CDK1 Inhibitors: Design, Synthesis, Biological Activity, and Molecular Docking Studies
Author(s) -
Raffa Demetrio,
Maggio Benedetta,
Cascioferro Stella,
Raimondi Maria Valeria,
Daidone Giuseppe,
Plescia Salvatore,
Schillaci Domenico,
Cusimano Maria Grazia,
Titone Lucina,
Colomba Claudia,
Tolomeo Manlio
Publication year - 2009
Publication title -
archiv der pharmazie
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.468
H-Index - 61
eISSN - 1521-4184
pISSN - 0365-6233
DOI - 10.1002/ardp.200800159
Subject(s) - cyclin dependent kinase 1 , chemistry , docking (animal) , indazole , stereochemistry , cell culture , kinase , molecular model , biochemistry , cytotoxic t cell , cell cycle , cell , in vitro , biology , genetics , medicine , nursing
A series of N ‐1 H ‐indazole‐1‐carboxamides has been synthesized and their effects on both CDK1 / cyclin B and the K‐562 (human chronic myelogenus leukemia) cell line were evaluated. Using a computational model, we have observed that all the most active compounds 9e , f , i – n exhibited the same binding mode of purvanalol A in the ATP‐binding cleft. Although they were able to moderately inhibit the leukemic cell line K‐562 and to show inhibitory activity against the Cdc2‐Cyclin B kinase in the low micromolar range, they turned out to be non‐cytotoxic against HuDe (IZSL) primary cell cultures from human derm. These preliminary results are quite encouraging in view of the low toxicity demonstrated by the above‐mentioned compounds.