Pyrazolo[3,4-h]quinolines promising photosensitizing agents in the treatment of cancer

作者：Spano Virginia; Parrino Barbara; Carbone Anna; Montalbano Alessandra; Salvador Alessia; Brun Paola; Vedaldi Daniela; Diana Patrizia; Cirrincione Girolamo; Barraja Paola^*

来源：European Journal of Medicinal Chemistry, 2015, 102: 334-351.

DOI：10.1016/j.ejmech.2015.08.003

• Pyrazolo[3,4-h]quinolines
• Photodynamic therapy
• Antiproliferative activity
• Photosensitizing agents
• Reactive oxygen species
• PUVA therapy

A new series of pyrazolo[3,4-h]quinolines, heteroanalogues of angelicin was conveniently prepared with a broad substitution pattern. A large number of derivatives was obtained and the cellular photocytotoxicity was evaluated in vitro against 5 different human tumor cell lines with GI(50) values reaching the nanomolar level (14.52-0.04 mu M). Selected compounds were able to photoinduce a massive cell death with the involvement of mitochondria. Their photodamage cellular targets were proteins and lipids and they did not cause any kind of DNA photodamage. This latter event is of considerable importance in the modulation of long term side effects, generally associated with the use of classical furocoumarins.

• 出版日期2015-9-18