Insights of Tris(2-pyridylmethyl)amine as anti-tumor agent for osteosarcoma: experimental and in silico studies

Publication: Journal of Molecular Structure
Software: ADMET Predictor®


Osteosarcoma (OS) is a malignant bone tumor and its occurrence is associated with high levels of microRNAs (miRNAs) and critical protein involved on intracellular signaling pathways. Cisplatin and Doxorubicin are employed on chemotherapy, but their use cause side effects and contributes to multidrug resistance. Since several tripodal amines have been studied as anticancer agents, tris(2-pyridylmethyl)amine (TPA) was investigated against osteosarcoma cells. Here we show that TPA exhibits activity against MG-63 and Saos-2 cells. Cyclic voltammetry results indicate an interaction between TPA and dsDNA, denoted by blocking of the proton-assisted reduction of the 2-pyridylmethyl moiety in the presence of the biomolecule. Molecular docking studies indicate binding modes between TPA and DNA, as well as other crucial biological targets related to OS pathology. In addition, ADMET in silico prediction results suggest a good pharmacokinetic and toxicity profile for TPA.

By Marcos V.Palmeira-Mello, Juliana Lima Souza, Anthuan Ferino Pérez, Amanda dos Santos Cavalcanti, Suzana Assad Kahn, Nady Passe-Coutrin, Idania Rodeiro Guerra, Antonio Doménech-Carbó, Ulises Javier Jauregui-Haza, Alessandra Mendonça Telesde Souza, Mauricio Lanznaster and Gerardo Cebrián-Torrejón