Introduction

A new method for the synthesis of psammapline A derivatives (UVI5000), of the 2-substituted indole-carboxamide type, a fast, simple method with high yields. This method is more effective than the approaches of Hoshino and Nicolaou; a new synthesis and molecules with increased antitumor action.

Technical features

Surprisingly, the inventors have discovered that the molecules responding to formula (Figure 1) can be use in the prevention and/or the treatment of cancer exploiting their peculiar properties:

• Induction cell cycle arrest
• Induction of apoptosis
• Inhibition of histone deacetylases (HDACs)
• Induction expression of the TNF-related apoptosis inducing ligand TRAIL.

In particular, the molecules of the invention UVI5008 and UVI5010 induced inhibition of proliferation and/or apoptosis in U937 acute myeloid leukemia cell line (Figure 2). Additionally, UVI5008 is a powerful inhibitor of DNA methyltransferase (DNMT) (Figure 3). Inhibits DNA methylation in the promoter region of the tumour suppressor genes p16^INK4a and RARb2 (Figure 4). The inventors speculate about UVI5008 as promising candidate anticancer drugs for its anti-proliferative activity and ability to restore the pharmacosensitivity.

Possible Applications

• HDACi;
• DNMTi;
• Anticancerdrug;
• Chemosensitizer.

Advantages

• Greater anti-cancer actions than known molecules;
• Possibility of use in prevention;
• Cell cycle regulation activity of derivatives;
• Inhibiting the activity of DNMT – UVI5008.