Introduction

Pyrazolo[3,4-h]quinolines, were prepared as photosensitizers for the treatment of hyperproliferative disorders in PDT. A large number of derivatives induced remarkable in vitro photocytotoxicity with GI50 values reaching the nanomolar level. Selected compounds were able to photoinduce a massive cell death with the involvement of mitochondria and did not cause any DNA damage. This latter event is of considerable importance in the modulation of long term side effects, generally associated with the use of classical furocoumarins.

Technical features

Photodynamic therapy (PDT), is a promising non invasive treatment for cancer and non malignant tumors. It has been used in clinical treatment for a long period for its minimal normal tissue toxicity, negligible systemic effects, greatly reduced long-term morbidity, lack of intrinsic or acquired resistance mechanisms. Clinical studies revealed that PDT can be curative, particularly in early stage tumors. It can prolong survival in patients with inoperable cancers and significantly improve quality of life. Its mechanism consists on the use of light to activate a tumor localized photosensitizer, selectively by destroying tumor tissue via the in situ generation of highly cytotoxic reactive oxygen species (ROS).

Possible Applications

• The new fused nitrogen heterocycles are promising photosensitizers in PDT for the treatment of infections;
• To treat hyperproliferative disorders such as psoriasis, vitiligo and cutaneous T-cell linphoma.

Advantages

• Compared to other cancer treatment modalities (surgery, radio- and chemo-therapy) PDT has the advantage of high selectivity to malignant target versus normal cells, and low damage;
• Pyrazolo[3,4-h]quinolines are small lipophilic molecules with remarkable photosensitizing properties;
• Extensive oxidative damage to mithocondria and membrane lipids without affecting DNA.