Introduction

Ceramide is a lipid messenger involved in controlling cell proliferation and death. An innovative approach in the treatment of cancer cells is the modulation of the levels of ceramide within them. Acid ceramidase is an enzyme that regulates the amount of intracellular ceramide. An increase in the activity of this enzyme causes the decrease in cellular levels of ceramide, which in turn accelerates the growth of cancer cells and increases their resistance capabilities. The use of acid ceramidase inhibitors has proven to be a very effective approach for the treatment of neoplasms and other disorders in which the modulation of ceramide levels is clinically relevant.

Technical features

In the literature there are some acid ceramidase inhibitors, but they are structurally similar to ceramides capable of inhibiting the activity of the enzyme in non-cellular assays and the proliferation of tumor cell lines only at high micromolar concentrations. There is therefore a substantial need to identify new acid ceramidase inhibitors with improved inhibitory potency and drug-like properties. The invention is based on the discovery that chemical compounds containing a uracilic nucleus inhibit acid ceramidase and by which a chemical formula has been derived. Compounds of this formula may be isolated as salts. In some embodiments, the compounds of the present invention can be combined as an active ingredient in intimate blend with a suitable pharmaceutical carrier and/or excipient according to conventional pharmaceutical compounding techniques. The compositions include various routes of administration, and each case will depend in part on the nature and severity of the conditions treated and the nature of the active substance. TRL2-3.

Possible Applications

• Treatment or prevention of a pathological condition such as cancer, tumor metastases, hyperplasia, metaplasia, dysplasia, hyperproliferative disorders, benign disproliferative disorders and psoriasis
• Use in combination with radiotherapy and/or an active ingredient, preferably an anti-cancer agent
• Treatment or prevention of a disease or disorder associated with acidic ceramidase overexpression

Advantages

• Powerful acid ceramidase inhibitors, both in vitro and in vivo experiments;
• Potentiators, chemosensitizers of the action of chemotherapeutic drugs and/or radiotherapy