Benzo[a]carbazole compounds and uses
Introduction
The invention relates to compounds of formula I where a proper combination of substituents produces a modulation of apoptosis by inhibition of complex MDM2-p53. The inhibition of MDM2-p53 interaction is a therapeutic target in cancer and immunology where a degradation of p53 can induce a pro-carcinogenic effect in host cells. RM37 is an example of compounds of formula I.
Technical features
The invention relates to compounds of formula I where a proper combination of substituents can confer a modulatory activity on apoptosis by inhibition of the binding between MDM2 (or MDMX) and the transcription factor p53. Degradation of p53 can induce a pro- carcinogenic effect in host cells. The inhibition of MDM2-p53 interaction is a therapeutic target in cancer and immunological diseases. Molecules I properly substituted can be used for therapeutic purposes but can be also functionalized to become diagnostic probes. RM37 is a representative example of molecules I, able to effectively bind the intracellular target MDM2 without having antibiotic activity and is characterized by a low toxicity for host cells.
Possible Applications
I as Chemotherapeutics or use of labelled derivatives of I as diagnostic probes in pathologies with loss of p53 activity or MDM2/X overexpression in:
- Oncology;
- Immunology;
- Haematology;
- Gastroenterology;
- Neurology;
- Cardiopulmonary diseases.
Advantages
- Potency and selectivity for the target (RM37 IC50 = 220 nM, Nutlin-3 IC50 = 290 nM);
- Low toxicity for host cells;
- Lack of antibiotic activity;
- Good bioavailability;
- Feasible synthetic process.