28022-03-9Relevant academic research and scientific papers
ALLOSTERIC INHIBITORS OF ATYPICAL PROTEIN KINASES C
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Paragraph 0090; 0108; 0141, (2015/06/08)
The invention provides specific small molecule compounds that allosterically regulate the activity of atypical protein kinase C, their use as a medicament, and their use in the treatment and prevention of allergic, inflammatory and autoimmune disorders, cancer, hyperproliferation, sepsis, viral and protozoan infections, dementing diseases, metabolic, sclerotic and osteoporotic disorders.
Antimycobacterial and anti-inflammatory activities of substituted chalcones focusing on an anti-tuberculosis dual treatment approach
Ventura, Thatiana Lopes Biá,Calixto, Sanderson Dias,De Azevedo Abrahim-Vieira, Bárbara,De Souza, Alessandra Mendon?a Teles,Mello, Marcos Vinícius Palmeira,Rodrigues, Carlos Rangel,De Mariz E Miranda, Leandro Soter,De Souza, Rodrigo Octavio Mendon?a Alves,Leal, Ivana Correa Ramos,Lasunskaia, Elena B.,Muzitano, Michelle Fraz?o
, p. 8072 - 8093 (2015/05/20)
Tuberculosis (TB) remains a serious public health problem aggravated by the emergence of M. tuberculosis (Mtb) strains resistant to multiple drugs (MDR). Delay in TB treatment, common in the MDR-TB cases, can lead to deleterious life-threatening inflammation in susceptible hyper-reactive individuals, encouraging the discovery of new anti-Mtb drugs and the use of adjunctive therapy based on anti-inflammatory interventions. In this study, a series of forty synthetic chalcones was evaluated in vitro for their anti-inflammatory and antimycobacterial properties and in silico for pharmacokinetic parameters. Seven compounds strongly inhibited NO and PGE2 production by LPS-stimulated macrophages through the specific inhibition of iNOS and COX-2 expression, respectively, with compounds 4 and 5 standing out in this respect. Four of the seven most active compounds were able to inhibit production of TNF-α and IL-1β. Chalcones that were not toxic to cultured macrophages were tested for antimycobacterial activity. Eight compounds were able to inhibit growth of the M. bovis BCG and Mtb H37Rv strains in bacterial cultures and in infected macrophages. Four of them, including compounds 4 and 5, were active against a hypervirulent clinical Mtb isolate as well. In silico analysis of ADMET properties showed that the evaluated chalcones displayed satisfactory pharmacokinetic parameters. In conclusion, the obtained data demonstrate that at least two of the studied chalcones, compounds 4 and 5, are promising antimycobacterial and anti-inflammatory agents, especially focusing on an anti-tuberculosis dual treatment approach.
Discovery and optimization of 1,3,5-trisubstituted pyrazolines as potent and highly selective allosteric inhibitors of protein kinase C-χ
Abdel-Halim, Mohammad,Diesel, Britta,Kiemer, Alexandra K.,Abadi, Ashraf H.,Hartmann, Rolf W.,Engel, Matthias
supporting information, p. 6513 - 6530 (2014/10/15)
There is increasing evidence that the atypical protein kinase C, PKCχ, might be a therapeutic target in pulmonary and hepatic inflammatory diseases. However, targeting the highly conserved ATP-binding pocket in the catalytic domain held little promise to
Solvent free synthesis of 1,3-diaryl-2-propenones catalyzed by commercial acid-clays under ultrasound irradiation
Chtourou, Manef,Abdelhédi, Rami,Frikha, Mohamed Hédi,Trabelsi, Mahmoud
experimental part, p. 246 - 249 (2010/11/16)
This paper presents a novel solvent free method of synthesis of trans-chalcones. The method was based on ultrasound irradiation of the reagents (aryl methyl ketones and aryl aldehydes) in presence of commercial acid-montmorillonites as catalysts. The trans-chalcones were synthesized in high yields (85-95%) and excellent selectivity in a short reaction time.
