Anti-cancer activities of a new family of ethacrynic acid derivatives

Remarkable advances have been made in the field of chemotherapy through the introduction of new molecules such as thalidomide, lenalidomide, and bortezomib. Despite this, cancer remains an incurable disease. The effectiveness of chemotherapy still needs improvement by reducing the toxicity and side effects of treatments. Furthermore, the intrinsic or acquired resistance of many tumors to chemotherapy is also a major obstacle to the efficacy of anticancer treatments. Several mechanisms of cellular resistance to different active substances have been identified (Moscow and Cowan 1988). Considering this, the search for new effective chemotherapy agents capable of treating various types of cancer is still indispensable

The present invention relates to a new class of small anti-cancer molecules derived from ethacrynic acid (symbolized by AE). The invention relates to the in vitro and in vivo anti-cancer activities and to the methods for producing the new AE family. New AE analogues were synthesized and then the in vitro cytotoxic activities thereof were evaluated on the P815 tumour cell line using the MTT test. The AE derivative which exhibited the best in vitro cytotoxicity was then tested in vivo using the DBA2/P815 (H₂d) mouse model. At 30 mg/kg, the effective dose, the animals showed general tolerance with a percentage survival of around 80%, and no significant weight loss was observed.