Novel Cancer Chemotherapy Hits by Molecular Topology: Dual XXXX and Beta-Catenin Inhibitors.

@entity5 @entity584 @entity3546 @entity3470 @entity14 @entity204
BACKGROUND AND PURPOSE: @entity14 are two of the most common types and cause of a high rate of @entity204 worldwide. Therefore, any strategy to stop or at least slacken the development and progression of malignant cells is an important therapeutic choice. The aim of the present work is the identification of novel @entity5 chemotherapy agents. Nowadays, many different drug discovery approaches are available, but this paper focuses on Molecular Topology, which has already demonstrated its extraordinary efficacy in this field, particularly in the identification of new hit and lead compounds against @entity5 . This methodology uses the graph theoretical formalism to numerically characterize molecular structures through the so called topological indices. Once obtained a specific framework, it allows the construction of complex mathematical models that can be used to predict physical, chemical or biological properties of compounds. In addition, Molecular Topology is highly efficient in selecting and designing new hit and lead drugs. According to the aforementioned, Molecular Topology has been applied here for the construction of specific @entity584 / @entity3470 and @entity3546 inhibition mathematical models in order to identify and select novel antitumor agents. EXPERIMENTAL APPROACH: Based on the results obtained by the selected mathematical models, six novel potential inhibitors of the @entity584 / @entity3470 and @entity3546 pathways were identified. These compounds were then tested in vitro to confirm their biological activity. CONCLUSION AND IMPLICATIONS: Five of the selected compounds, CAS n   256378-54-8 (Inhibitor n  1), 663203-38-1 (Inhibitor n  2), 247079-73-8 (Inhibitor n  3), 689769-86-6 (Inhibitor n  4) and 431925-096 (Inhibitor n  6) gave positive responses and resulted to be active for @entity584 / @entity3470 and/or @entity3546 inhibition. This study confirms once again the Molecular Topology's reliability and efficacy to find out novel drugs in the field of @entity5 .
