Journal
JOURNAL OF MOLECULAR STRUCTURE
Volume 1228, Issue -, Pages -Publisher
ELSEVIER
DOI: 10.1016/j.molstruc.2020.129773
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- Coordenacao de Aperfeicoamento de Pessoal de Nivel Superior - Brazil (CAPES) [001]
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Osteosarcoma is a rare malignant bone tumor with high levels of microRNAs and key proteins involved in intracellular signaling pathways. Chemotherapy with Cisplatin and Doxorubicin can cause side effects and drug resistance. The tri(2-pyridylmethyl)amine shows potential activity against osteosarcoma cells by interacting with DNA and other biological targets.
Osteosarcoma (OS) is a malignant bone tumor and its occurrence is associated with high levels of microRNAs (miRNAs) and critical protein sinvolved 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 MG63 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. (C) 2020 Elsevier B.V. All rights reserved.
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