255833-23-9Relevant articles and documents
Synthesis and structure-activity relationships of novel, potent, orally active hypoxia-inducible factor-1 inhibitors
Nagao, Satoshi,Yamane, Yoshinobu,Funasaka, Setsuo,Tanaka, Keigo,Miyazaki, Kazuki,Kotake, Yoshihiko,Kamata, Jun-Ichi,Watanabe-Miyano, Saori,Toyama, Osamu,Ozawa, Yoichi,Mizui, Yoshiharu,Okamoto, Kiyoshi,Ito, Daisuke
, p. 5513 - 5529 (2014/12/10)
Hypoxia-inducible factor-1 (HIF-1) is the chief transcription factor regulating hypoxia-driven gene expression. HIF-1 overexpression is associated with poor prognosis in several cancers and therefore represents an attractive target for novel antitumor agents. We explored small molecule inhibitors of the HIF-1 pathway. Using high-throughput-screening, we identified benzanilide compound 1 (IC50= 560 nM) as a seed. Subsequent extensive derivatization led to the discovery of compounds 43a and 51d, with anti-HIF-1 activities in vitro (IC50= 21 and 0.47 nM, respectively), and in vivo. Additionally, 43a (12.5-100 mg/kg) also displayed in vivo anti-tumor efficacy, without influencing body weight.
Identification of 5-arylidene-4-thiazolidinone derivatives endowed with dual activity as aldose reductase inhibitors and antioxidant agents for the treatment of diabetic complications
Ottanà, Rosaria,MacCari, Rosanna,Giglio, Marco,Del Corso, Antonella,Cappiello, Mario,Mura, Umberto,Cosconati, Sandro,Marinelli, Luciana,Novellino, Ettore,Sartini, Stefania,La Motta, Concettina,Da Settimo, Federico
experimental part, p. 2797 - 2806 (2011/07/08)
In continuing the search for more effective 5-arylidene-4-thiazolidinones as aldose reductase inhibitors, a new set of suitably substituted compounds (4, 5 and 8) was explored. Acetic acids 5, particularly 5a and 5h, proved to be interesting inhibitors of the enzyme as well as excellent antioxidant agents that are potentially able to counteract the oxidative stress associated with both diabetic complications as well as other pathologies. Molecular docking experiments supported SAR studies.
