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

• Broadly decorated pyrazolo[3,4-h]quinolines were conveniently prepared.
• Strong phototoxic activity with GI50 values reaching nanomolar level was detected.
• No DNA photodamage was induced, relevant for the modulation of side effects.

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 GI50 values reaching the nanomolar level (14.52–0.04 μM). 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.

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 GI50 values reaching the nanomolar level (14.52–0.04 μM). Selected compounds were able to photoinduce a massive cell death with the involvement of mitochondria. Their photodamage cellular targets were proteins and lipids and 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.Figure optionsDownload as PowerPoint slide