Pyrrolo[3',2':6,7]cyclohepta[1,2-b]pyridines with potent photo-antiproliferative activity.

European journal of medicinal chemistry 2017 Mar 10

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Pyrrolo[3',2':6,7]cyclohepta[1,2-b]pyridines were synthesized as a new class of tricyclic system in which the pyridine ring is annelated to a cycloheptapyrrole scaffold, with the aim of obtaining new photosensitizing agents with improved antiproliferative activity and lower undesired toxic effects. A versatile synthetic pathway was approached, which allowed the isolation of derivatives of the title ring system with a good substitution pattern on the pyrrole moiety. Photobiological studies revealed that the majority of the new compounds showed a potent cytotoxic effect upon photoactivation with light of the proper wavelength, especially when decorated with a 2-ethoxycabonyl group and a N-benzyl substituted moiety, with EC50 values reaching the submicromolar level. The mechanism of action was evaluated. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

Citation

Virginia Spanò, Daniele Giallombardo, Vincenzo Cilibrasi, Barbara Parrino, Anna Carbone, Alessandra Montalbano, Ilaria Frasson, Alessia Salvador, Sara N Richter, Filippo Doria, Mauro Freccero, Stella Cascioferro, Patrizia Diana, Girolamo Cirrincione, Paola Barraja. Pyrrolo[3',2':6,7]cyclohepta[1,2-b]pyridines with potent photo-antiproliferative activity. European journal of medicinal chemistry. 2017 Mar 10;128:300-318