Garcia da Silva, Artur Christian; Rodrigues, Bruna dos Santos; Andrade, Wanessa Machado; Marques dos Santos, Thais Rosa; de Carvalho, Flavio Silva; Sanz, German; Vaz, Boniek G.; Liao, Luciano M.; Menegatti, Ricardo; Valadares, Marize Campos published the artcile< Antiangiogenic and antitumoral activity of LQFM126 prototype against B16F10 melanoma cells>, Computed Properties of 13788-92-6, the main research area is Nutlin analog antiangiogenic antitumoral agent melanoma cell; Antitumor drugs; Apoptosis; LQFM126; Melanoma; Molecular simplification; Nutlins.
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 mol. 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. Addnl., 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.
Chemico-Biological Interactions published new progress about Angiogenesis. 13788-92-6 belongs to class pyrazoles-derivatives, and the molecular formula is C9H7BrN2, Computed Properties of 13788-92-6.
Referemce:
Pyrazole – Wikipedia,
Pyrazoles – an overview | ScienceDirect Topics