This technology concerns to the application of new compounds with a potent anti-parasite activity against leishmaniasis causing organisms, as well as anti-cancer activity: Bisnaphthalimidopropyl (BNIP) derivatives.
Naphthalimido derivatives exhibit considerable potential anti-parasite activity. They also exhibit considerable potential as cytotoxic agents for cancer therapy. To realise these potential and to enhance the activity of such compounds, most previous research has been focused on the modification of the naphthalimido ring structure through increased DNA binding and cleavage. We have now created a number of new bisnapthalimidopropyl (BNIP) derivatives characterised by the use of natural polyamine linkers between the BNIP fragments. The family of new derivatives differ in respect of their respective alkyl linker chain lengths and nitrogen atom content. Compared to previous derivatives, these compounds have enhanced water solubility and now show potent in vitro and in vivo anti-proliferative effects on the life cycle of the protozoans Leishmania infantum, Trypanosoma brucei and T. cruzi, the causative agents of leishmaniasis, sleeping disease and Chagas disease, respectively, in humans. At the anti-cancer activity level, these compounds retain their cytotoxic potency against a number of human tumour cells cultured in vitro and in vivo.
- Natural polyamine structures are the basis of the BNIP derivatives with alkyl linker chains;
- Enhanced water solubility due to the alkyl chain length and charge distribution;
- High yeild chemical synthetic strategies established;
- Advanced nanoformulation technologies compatibility;
- Potent in vitro and in vivo anti-trypanosomal (anti-Leishmania, anti-T.brucei and anti-T. cruzi) activity;
- Cytotoxicity to human pancreatic adenocarcinoma cells, inducing an apopotic cell death (in vitro);
- Reduction of the tumour cell growth (in vivo).