2023-08-012023-08-012020SILVA, 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.e- 1872-77860009-2797https://www.sciencedirect.com/science/article/abs/pii/S000927972030404X?via%3DihubInhibition 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.engAcesso RestritoArtigo10.1016/j.cbi.2020.109127