Antiangiogenic and antitumoral activity of LQFM126 prototype against B16F10 melanoma cells
dc.creator | Silva, Artur Christian Garcia da | |
dc.creator | Rodrigues, Bruna dos Santos | |
dc.creator | Andrade, Wanessa Machado | |
dc.creator | Santos, Thaís Rosa Marques dos | |
dc.creator | Flávio Silva de Carvalho | |
dc.creator | Sanz Lobón, Germán | |
dc.creator | Vaz, Boniek Gontijo | |
dc.creator | Liao, Luciano Morais | |
dc.creator | Menegatti, Ricardo | |
dc.creator | Valadares, Marize Campos | |
dc.date.accessioned | 2023-08-01T15:51:19Z | |
dc.date.available | 2023-08-01T15:51:19Z | |
dc.date.issued | 2020 | |
dc.description.abstract | Inhibition 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.citation | SILVA, 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.doi | 10.1016/j.cbi.2020.109127 | |
dc.identifier.issn | e- 1872-7786 | |
dc.identifier.issn | 0009-2797 | |
dc.identifier.uri | https://www.sciencedirect.com/science/article/abs/pii/S000927972030404X?via%3Dihub | |
dc.language.iso | eng | pt_BR |
dc.publisher.country | Holanda | pt_BR |
dc.publisher.department | Instituto de Química - IQ (RMG) | pt_BR |
dc.rights | Acesso Restrito | pt_BR |
dc.title | Antiangiogenic and antitumoral activity of LQFM126 prototype against B16F10 melanoma cells | pt_BR |
dc.type | Artigo | pt_BR |
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