- Antiangiogenic and antitumoral activity of LQFM126 prototype against B16F10 melanoma cells
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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.
- Andrade, Wanessa Machado,Garcia da Silva, Artur Christian,Menegatti, Ricardo,Rodrigues, Bruna dos Santos,Valadares, Marize Campos,Vaz, Boniek G.,Li?o, Luciano M.,Marques dos Santos, Thaís Rosa,Sanz, Germán,de Carvalho, Flávio Silva
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- Electrophotocatalytic SNAr Reactions of Unactivated Aryl Fluorides at Ambient Temperature and Without Base
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The electrophotocatalytic SNAr reaction of unactivated aryl fluorides at ambient temperature without strong base is demonstrated.
- Huang, He,Lambert, Tristan H.
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supporting information
p. 658 - 662
(2019/11/28)
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- BIARYL DERIVATIVE AS GPR120 AGONIST
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The present invention relates to a biaryl derivative expressed by the chemical formula 1, a method for producing the biaryl derivative, a pharmaceutical composition comprising same, and use of same, the biaryl derivative expressed by the chemical formula 1, as a GPR120 agonist, promoting GLP-1 generation in the gastro-intestinal tract, reducing insulin resistance in the liver, muscles and the like from anti-inflammatory activity in the macrophage, pancreatic cells and the like, and allowing effective use in prevention or treatment of inflammation or metabolic diseases such as diabetes, complications from diabetes, obesity, non-alcoholic fatty liver disease, fatty liver disease, and osteoporosis.
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- TRIAZOLOPYRIDINE INHIBITORS OF MYELOPEROXIDASE
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The present invention provides compounds of Formula (I): wherein A is as defined in the specification, and compositions comprising any of such novel compounds. These compounds are myeloperoxidase (MPO) inhibitors and/or eosinophil peroxidase (EPX) inhibitors, which may be used as medicaments.
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Paragraph 00212
(2017/03/28)
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- Chemoselective and regiospecific formylation of 1-phenyl-1H-pyrazoles through the duff reaction
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The synthesis of formylated 1-phenyl-1H-pyrazole derivatives under the Duff reaction conditions is reported. Our results indicate that 1-phenyl-1H-pyrazole systems containing electron-withdrawing and electron-donating substituents at the phenyl moiety rea
- De Oliveira,Mairink,Pazini,Liao,De Oliveira,Viegas Jr.,De Oliveira,Cunha,Oliveira,Paz Jr.,Eberlin,Menegatti, Ricardo
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supporting information
p. 1633 - 1639
(2013/05/22)
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- Complete assignment of NMR data of 22 phenyl-1H-pyrazoles' derivatives
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Complete assignment of 1H and 13C NMR chemical shifts and J(1H/1H and 1H/19F) coupling constants for 22 1-phenyl-1H-pyrazoles' derivates were performed using the concerted application of 1H 1D and 1H, 13C 2D gs-HSQC and gs-HMBC experiments. All 1-phenyl-1H-pyrazoles' derivatives were synthesized as described by Finar and co-workers. The formylated 1-phenyl-1H-pyrazoles' derivatives were performed under Duff's conditions. Copyright
- De Oliveira, Aline Lima,Alves De Oliveira, Carlos Henrique,Mairink, Laura Maia,Pazini, Francine,Menegatti, Ricardo,Liao, Luciano Morais
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scheme or table
p. 537 - 542
(2011/10/09)
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- Synthesis and antileishmanial activity of new 1-aryl-1H-pyrazole-4- carboximidamides derivatives
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Chemotherapy for leishmaniasis, diseases caused by protozoa of the genus Leishmania, remains inefficient in several treatments. So there is a need to search for new drugs. In this work, we have synthesized 1-aryl-1H-pyrazole-4- carboximidamides derivatives and evaluated antileishmanial activities in vitro, as well as cytotoxic effects. Structure-activity relationship (SAR) studies were carried out with all the compounds of the series. Compound 2 showed an activity profile that can be improved through medicinal chemistry strategies.
- Dos Santos, Mauri?cio S.,Gomes, Adriana O.,Bernardino, Alice M. R.,De Souza, Marcos C.,Khan, Misbahul A.,De Brito, Monique A.,Castro, Helena C.,Abreu, Paula A.,Rodrigues, Carlos R.,De Le?o, Rosa M. M.,Leon, Leonor L.,Canto-Cavalheirr, Marilene M.
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experimental part
p. 352 - 358
(2011/10/04)
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