39229-58-8Relevant articles and documents
LASSBio-1586, an N-acylhydrazone derivative, attenuates nociceptive behavior and the inflammatory response in mice
Silva, Juliane Cabral,De Oliveira, Raimundo Gon?alves,e Silva, Mariana Gama,De Lavor, érica Martins,Soares, Juliana Mikaelly Dias,De Lima-Saraiva, Sarah Raquel Gomes,Diniz, Tamara Coimbra,Mendes, Rosemairy Luciane,De Alencar Filho, Edilson Beserra,De Lacerda Barreiro, Eliezer Jesus,Lima, Lídia Moreira,Da Silva Almeida, Jackson Roberto Guedes
, (2018/08/06)
Pain and inflammation are complex clinical conditions that are present in a wide variety of disorders. Most drugs used to treat pain and inflammation have potential side effects, which makes it necessary to search for new sources of bioactive molecules. In this paper, we describe the ability of LASSBio-1586, an N-acylhydrazone derivative, to attenuate nociceptive behavior and the inflammatory response in mice. Antinociceptive activity was evaluated through acetic acid-induced writhing and formalin-induced nociception tests. In these experimental models, LASSBio-1586 significantly (p0.05) reduced nociceptive behavior. Several methods of acute and chronic inflammation induced by different chemical (carrageenan, histamine, croton oil, arachidonic acid) and physical (cotton pellet) agents were used to evaluate the anti-inflammatory effect of LASSBio-1586. LASSBio-1586 exhibited potent anti-inflammatory activity in all tests (p0.05). Study of the mechanism of action demonstrated the possible involvement of the nitrergic, serotonergic and histamine signaling pathways. In addition, a molecular docking study was performed, indicating that LASSBio-1586 is able to block the COX-2 enzyme, reducing arachidonic acid metabolism and consequently decreasing the production of prostaglandins, which are important inflammatory mediators. In summary, LASSBio-1586 exhibited relevant antinociceptive and anti-inflammatory potential and acted on several targets, making it a candidate for a new multi-target oral anti-inflammatory drug.
ACYL-HYDRAZONE AND OXADIAZOLE COMPOUNDS, PHARMACEUTICAL COMPOSITIONS CONTAINING THE SAME AND USES THEREOF
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, (2014/10/15)
The present invention relates to acyl-hydrazone compounds, in particular 3,4,5-trimethoxyphenyl-hydrazide derivatives, as well as the oxadiazole analogs thereof and other similar compounds, and to the pharmaceutical use of the same for the treatment of various diseases associated with cell proliferation, such as leukemias, including acute lymphoblastic leukemia (ALL), tumours and inflammation. Acyl-hydrazones have been obtained having activity similar to that of the compound used as a standard in experiments (colchicine). The greater selectivity of the compounds according to the invention is an important feature, associated with fewer side effects than the pharmaceuticals used at present in clinical treatments. The synthetised acyl-hydrazones, more particularly the compounds 02 and 07, exhibited important anti-leukemic activity, which suggests 02 and 07 as candidates to pharmaceutical prototypes, or to pharmaceuticals for the treatment of leukemias, in particular acute lymphoblastic leukemia (ALL), tumours and other proliferative diseases, such as inflammation. The action mechanism of the most active compounds was determined by using DNA microarrays and subsequent tests indicated by the chip, besides selectivity studies in healthy human lymphocytes.
Design, synthesis, and biological evaluations of 2,5-diaryl-2,3-dihydro-1, 3,4-oxadiazoline analogs of combretastatin-A4
Lee, Lauren,Robb, Lyda M.,Lee, Megan,Davis, Ryan,Mackay, Hilary,Chavda, Sameer,Babu, Balaji,O'Brien, Erin L.,Risinger, April L.,Mooberry, Susan L.,Lee, Moses
experimental part, p. 325 - 334 (2010/05/02)
A total of 24 novel 2,5-diaryl-1,3,4-oxadiazoline analogs of combretastatin A-4 (CA-4, 1) were designed, synthesized, and evaluated for biological activities. The compounds represent two structural classes; the Type I class has three methoxy groups on the A ring and the Type II class has a single methoxy group on the A ring. Biological evaluations demonstrate that multiple structural features control the biological potency. Four of the compounds, 2-(3′-bromophenyl)-5-(3″,4″,5″-trimethoxyphenyl) -2-acetyl-2,3-dihydro-1,3, 4-oxadiazoline (91), 2-(2′,5′- dimethoxyphenyl)-5-(3″-methoxyphenyl)-2-acetyl-2,3-dihydro-1,3, 4-oxadiazoline (10h), 2-(3′,4′,5′-trimethoxyphenyl)-5- (3″-methoxyphenyl)-2-acetyl-2,3-dihydro-1,3,4-oxadiazoline (10i), and 2-(3′,5′-dimethoxyphenyl)-5-(3″-methoxyphenyl)-2-acetyl-2, 3-dihydro-1,3,4-oxadiazoline (10j), have potent antiproliferative activities against multiple cancer cell lines. Mechanistic studies indicate that they retain the microtubule disrupting effects of compound 1, including microtubule loss, the formation of aberrant mitotic spindles, and mitotic arrest. Compound 10i inhibits purified tubulin polymerization and circumvents drug resistance mediated by P-glycoprotein and βIII tubulin expression. The oxadiazoline analog 10i is a promising lead candidate worthy of further investigation.
