Antiangiogenic and antitumoral activity of LQFM126 prototype against B16F10 melanoma cells

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dc.creatorSilva, Artur Christian Garcia da
dc.creatorRodrigues, Bruna dos Santos
dc.creatorAndrade, Wanessa Machado
dc.creatorSantos, Thaís Rosa Marques dos
dc.creatorFlávio Silva de Carvalho
dc.creatorSanz Lobón, Germán
dc.creatorVaz, Boniek Gontijo
dc.creatorLiao, Luciano Morais
dc.creatorMenegatti, Ricardo
dc.creatorValadares, Marize Campos
dc.date.accessioned2023-08-01T15:51:19Z
dc.date.available2023-08-01T15:51:19Z
dc.date.issued2020
dc.description.abstractInhibition of mouse double minute 2 homolog (MDM2)-p53 interaction and reactivation of p53 signaling have been explored as effective anticancer therapeutic strategy. The potent and specific antitumor activity shown by Nutlins, first class of MDM2-p53 inhibitors discovered, has made these compounds potential antitumor candidates. To this end, we synthesized Nutlin-1 and Nutlin-2 analogs through molecular simplification and selected the compound with the most efficient antitumoral activity. Cytotoxicity of Nutlin-2 analog LQFM126 on B16F10 melanoma cells induced intense cytoplasmic vacuolization, reduction of cell size, chromatin condensation, cytoplasmic degeneration and nuclear fragmentation. LQFM126 antiproliferative effects mediated cell cycle retention in G0/G1 phase and increased the levels of cell cycle regulatory proteins p21 and p27. This Nutlin analog increased mitochondrial membrane potential, activated caspase-8, -9 and -3/7 and reduced VEGF levels in B16F10 cells. Therefore, LQFM126 promoted alterations suggestive of apoptosis, G0/G1 cell cycle arrest and suppression of angiogenesis through modulation of VEGF expression in B16F10 cells. Additionally, LQFM126 was classified as UN GHS category 4 (LD50 > 300–2000 mg/kg), suggesting it has low acute systemic toxicity. LQFM126 can be a promising prototype for anticancer therapy.pt_BR
dc.identifier.citationSILVA, Artur Christian Garcia da et al. Antiangiogenic and antitumoral activity of LQFM126 prototype against B16F10 melanoma cells. Chemico-Biological Interactions, Amsterdam, v. 325, e109127, 2020. DOI: 10.1016/j.cbi.2020.109127. Disponível em: https://www.sciencedirect.com/science/article/abs/pii/S000927972030404X?via%3Dihub. Acesso em: 21 jun. 2023.pt_BR
dc.identifier.doi10.1016/j.cbi.2020.109127
dc.identifier.issne- 1872-7786
dc.identifier.issn0009-2797
dc.identifier.urihttps://www.sciencedirect.com/science/article/abs/pii/S000927972030404X?via%3Dihub
dc.language.isoengpt_BR
dc.publisher.countryHolandapt_BR
dc.publisher.departmentInstituto de Química - IQ (RMG)pt_BR
dc.rightsAcesso Restritopt_BR
dc.titleAntiangiogenic and antitumoral activity of LQFM126 prototype against B16F10 melanoma cellspt_BR
dc.typeArtigopt_BR

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