Antitumor effect of chiral organotelluranes elicited in a murine melanoma model

Autor(es)

Paschoalin, Thaysa ; Martens, Adam A. ; Omori, Alvaro T. ; Pereira, Felipe V. ; Juliano, Luiz ; Travassos, Luiz R. ; Machado-Santelli, Glaucia M. ; Cunha, Rodrigo L. O. R.

• Tipo de documento: Artigo Científico
• Fonte: Bioorganic & Medicinal Chemistry; v. 27, n. 12, p. 9-pg., 2019-06-15.

Resumo

Protease roles in cancer progression have been demonstrated and their inhibitors display antitumor effects. Cathepsins are lysosomal cysteine proteases that have increased expression in tumor cells, and tellurium compounds were described as potent cysteine protease inhibitors and also assayed in several animal models. In this work, the two enantiomeric forms of 1-[Butyl(dichloro)-lambda(4)-tellanyl]-2-[1S-methoxyethyl]benzene (organotelluranes RF-13R and RF-13S) were evaluated as inhibitors of cathepsins B and L, showing significant enantiodiscrimination. We observed their cytotoxic effects on a murine melanoma model, effectively inhibiting tumor progression in vivo. The enantiomers were able to inhibit melanoma cell viability, migration and invasion in vitro. Besides, RF-13S and RF-13R were able to inhibit endothelial cell angiogenesis using a tube formation assay in vitro, in a stereodependent manner. These organotelluranes affected cell morphology, showing disassembling of the actin cytoskeleton. These results suggest organotelluranes as potential antitumor agents, acting directly on tumor cell proliferation, migration and invasion, and on endothelial cells, disrupting angiogenesis, showing low toxicity and high efficiency. Taken together our results suggest that this class of compounds should be further studied to reveal their potential as antitumoral agents. (AU)

• Processo FAPESP: 04/14426-0 - Desenvolvimento e aplicacao de novos inibidores de cisteino-proteases baseados em compostos alquilantes heterociclicos e em compostos organicos de selenio e de telurio.
• Beneficiário: Rodrigo Luiz Oliveira Rodrigues Cunha
• Modalidade de apoio: Bolsas no Brasil - Pós-Doutorado
• Processo FAPESP: 06/51880-7 - Identificacao dos moduladores proteoliticos e peptidicos da angiogenese no melanoma murino b16f1o-nex2 e possivel relevancia evolucao tumoral.
• Beneficiário: Thaysa Paschoalin
• Modalidade de apoio: Bolsas no Brasil - Pós-Doutorado
• Processo FAPESP: 09/53840-0 - Sistema de fluorescência para investigações dos aspectos fisiológicos e fisiopatológicos em modelos celulares
• Beneficiário: Adriana Karaoglanovic Carmona
• Modalidade de apoio: Auxílio à Pesquisa - Programa Equipamentos Multiusuários