Escuela Superior de Medicina- IPN, Mexico
Title: An approach to anti-cancer therapy with multitargeting ligands
José G Trujillo-Ferrara, a pioneer in Mexico in the fi eld of Medicinal Chemistry has focused on the rational drug design based on the molecular mechanisms of pathology. Experiments are done in vitro, in vivo and in silico to predict which compound will have the greatest effect in clinical use. He has authored more than 100 publications and has more than 600 citations. He is a member of the National System of Researchers II and a Board Editor of the Journal of Enzyme Inhibition and Medicinal Chemistry. He has been the advisor for 62 students to obtain a scholar degree.
Today the most common target of chemotherapy ligands that aim to avoid cell proliferation is a direct attack on DNA. Th is focus has a major drawback, which is that the DNA of cancer and healthy cells is the same, meaning that the therapy is not selective and it’s necessary to use several diff erent compounds. Th e epigenetic is aimed at the DNA environment and not a direct attack on DNA. Th is was the focus of the last contribution, which aim was to synthesize pro-apoptotic molecules that are α,β-unsaturated aryl amides, these compounds are highly selective for thiol-containing compounds, which are abundant in cancer cells. By targeting the DNA environment, cancer cells can be made more sensitive to attack by histone deacetlylaseinhibitors and ornithine decarboxylase-inhibitors. Th e aim of this contribution was to design a dual targeting molecule that inhibits both ornithine decarboxylase (ODC) and histone deacetylase (HDAC). Actually, we found two molecules that serve this purpose; these molecules are ω-chloroacetyl ornithine and ω-chloroacetyl lysine. Th ese molecules were tested in silico and in vitro. In both molecules docking clearly showed that the carboxylic moiety is the binding site of ODC while the chloroacetyl moiety is the binding site of HDAC. Th e in vitro studies showed an inhibition constant of 1.5 μM for both ODC and HDAC. Th e eff ect of both molecules was determined on three diff erent cell lines: Vero, HeLa, and Hep G2 cells. Th e results clearly show time-dependent and concentration-dependent inhibition of proliferation of cancer cells without any eff ect on healthy cells.