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

Eur J Med Chem. 2015 Sep 18:102:334-51. doi: 10.1016/j.ejmech.2015.08.003.

Virginia Spanò ¹, Barbara Parrino ¹, Anna Carbone ¹, Alessandra Montalbano ¹, Alessia Salvador ², Paola Brun ³, Daniela Vedaldi ², Patrizia Diana ¹, Girolamo Cirrincione ¹, Paola Barraja ⁴

Affiliations

1 Dipartimento di Scienze e Tecnologie Biologiche Chimiche e Farmaceutiche (STEBICEF), Università degli Studi di Palermo, Via Archirafi 32, 90123 Palermo, Italy.
2 Dipartimento di Scienze del Farmaco, Università degli Studi di Padova, Via Marzolo 5, 35131 Padova, Italy.
3 Dipartimento di Medicina Molecolare, Università degli Studi di Padova, Via Gabelli 63, 35121 Padova, Italy.
4 Dipartimento di Scienze e Tecnologie Biologiche Chimiche e Farmaceutiche (STEBICEF), Università degli Studi di Palermo, Via Archirafi 32, 90123 Palermo, Italy. Electronic address: paola.barraja@unipa.it.

PMID: 26295175 DOI: 10.1016/j.ejmech.2015.08.003

Abstract

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.

Keywords

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

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