Identification of a Novel p53 Modulator Endowed with Antitumoural and Antibacterial Activity through a Scaffold...

Area of Science:

• Oncology
• Infectious Diseases
• Molecular Biology

Background:

• Intracellular pathogens like Chlamydia trachomatis degrade p53, hindering host cell defense mechanisms.
• Reactivating p53 by disrupting the p53-MDM2 complex offers a strategy to combat infections and restore apoptosis.

Purpose of the Study:

• To identify a novel MDM2 inhibitor with potential anticancer and antibacterial properties.
• To evaluate the efficacy of the identified compound in reactivating p53 and combating Chlamydia infection.

Main Methods:

• Virtual screening of a chemical library to identify MDM2 inhibitors.
• Utilized U343MG glioblastoma and HeLa cells for in vitro studies.
• Employed NMR spectroscopy to confirm MDM2-p53 complex dissociation.

Main Results:

• Identified RM37, a benzo[a]dihydrocarbazole derivative, as a potent MDM2 inhibitor.
• RM37 induced p53 upregulation in glioblastoma cells, inhibiting tumor growth.
• RM37 demonstrated concentration-dependent reduction of Chlamydia infection and ameliorated inflammation.

Conclusions:

• RM37 effectively reactivates p53 by inhibiting MDM2-p53 interaction.
• The compound exhibits dual therapeutic potential against glioblastoma and Chlamydia infections.
• RM37 represents a promising candidate for developing novel treatments for cancer and infectious diseases.