99514-87-1Relevant academic research and scientific papers
Novel Symmetrical Benzazolyl Derivatives Endowed with Potent Anti-Heparanase Activity
Messore, Antonella,Madia, Valentina Noemi,Pescatori, Luca,Saccoliti, Francesco,Tudino, Valeria,De Leo, Alessandro,Bortolami, Martina,De Vita, Daniela,Scipione, Luigi,Pepi, Federico,Costi, Roberta,Rivara, Silvia,Scalvini, Laura,Mor, Marco,Ferrara, Fabiana Fosca,Pavoni, Emiliano,Roscilli, Giuseppe,Cassinelli, Giuliana,Milazzo, Ferdinando M.,Battistuzzi, Gianfranco,Di Santo, Roberto,Giannini, Giuseppe
, p. 10834 - 10859 (2019/01/03)
Heparanase is the only mammalian endo-β-d-glucuronidase involved in a variety of major diseases. The up-regulation of heparanase expression increases tumor size, angiogenesis, and metastasis, representing a validated target in the anti-cancer field. To date, only a few small-molecule inhibitors have been described, but none have gotten through pre-clinical development. Previously, we explored 2-(4-(4-(bromo-methoxybenzamido)benzylamino)phenyl) benzazole derivatives as anti-heparanase agents, proposing this scaffold for development of broadly effective heparanase inhibitors. Herein, we report an extended investigation of new symmetrical 2-aminophenyl-benzazolyl-5-acetate derivatives, proving that symmetrical compounds are more effective than asymmetrical analogues, with the most-potent compound, 7g, being active at nanomolar concentration against heparanase. Molecular docking studies were performed on the best-acting compounds 5c and 7g to rationalize their interaction with the enzyme. Moreover, invasion assay confirmed the anti-metastatic potential of compounds 5c, 7a, and 7g, proving the inhibition of the expression of proangiogenic factors in tumor cells.
Tri- and tetrasubstituted pyridinylimidazoles as covalent inhibitors of c-Jun N-terminal kinase 3
Muth, Felix,El-Gokha, Ahmed,Ansideri, Francesco,Eitel, Michael,D?ring, Eva,Sievers-Engler, Adrian,Lange, Andreas,Boeckler, Frank M.,L?mmerhofer, Michael,Koch, Pierre,Laufer, Stefan A.
, p. 594 - 607 (2017/02/05)
The concept of covalent inhibition of c-Jun N-terminal kinase 3 (JNK3) was successfully transferred to our well validated pyridinylimidazole scaffold varying several structural features in order to deduce crucial structure-activity relationships. Joint ta
