- Structural isomers of cinnamic hydroxamic acids block HCV replication via different mechanisms
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A set of ortho-, meta- and para-substituted cinnamic hydroxamic acids (CHAs) was synthesized. In each series of structural isomers, a phenyl substituent was linked to an aromatic ring of the parent cinnamic acid via a linker of one to four atoms in length
- Kozlov, Maxim V.,Konduktorov, Konstantin A.,Malikova, Alsu Z.,Kamarova, Kamila A.,Shcherbakova, Anastasia S.,Solyev, Pavel N.,Kochetkov, Sergey N.
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- Synthesis and Structure–Activity Relationships of Novel Benzylamine-Type Antifungals as Butenafine-Related Antimycotics
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Benzylamine-type antimycotics like naftifine, butenafine, or terbinafine are a well-known class of antimycotics since the 1980s. The following paper describes the synthesis and biological evaluation of a series of novel benzylamine-type antimycotics characterized by an isooctyl side chain and various substituents at the benzylamine moiety. The compounds were prepared from benzaldehyde derivatives and 2-amino-6-methylheptane by reductive amination with sodium triacetoxyborohydride and subsequent precipitation with hydrogen chloride. The antimycotic activity of the resulting compounds was evaluated in an agar diffusion assay against the yeasts C. glabrata and Yarrowia lipolytica, the mold Aspergillus niger and the dermatophyte H. burtonii. The compounds were also tested in a microdilution assay against the yeast Candida glabrata and the dermatophyte H. burtonii to determine the minimal inhibitory concentrations (MIC). Compounds with an aromatic ether side chain or a short alkyl ether side chain showed significant antimycotic activity against C. glabrata, comparable to terbinafine or clotrimazole.
- Krauss, Jürgen,Stadler, Martina,Bracher, Franz
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- Synthesis, biological activity and structure-activity relationships of new benzoic acid-based protein tyrosine phosphatase inhibitors endowed with insulinomimetic effects in mouse C2C12 skeletal muscle cells
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Insulin resistance is a complex altered metabolic condition characterized by impaired insulin signaling and implicated in the pathogenesis of serious human diseases, such as diabetes, obesity, neurodegenerative pathologies. In pursuing our aim to identify new agents able to improve cellular insulin sensitivity, we have synthesized new 4-[(5-arylidene-4-oxo-2-phenylimino/ oxothiazolidin-3-yl)methyl]benzoic acids (5, 8) and evaluated their inhibitory activity towards human protein tyrosine phosphatases PTP1B, LMW-PTP and TCPTP, enzymes which are involved in the development of insulin resistance. Compounds 5 and 8 showed from moderate to significant selectivity toward PTP1B over both the highly homologous TCPTP and the two isoforms of human LMW-PTP. In addition, most of the tested compounds selectively inhibited LMW-PTP IF1 over the isoform IF2. Docking studies into the active sites of PTP1B and LMW-PTP aided the rationalization of the observed PTP inhibitory profile. Moreover, most tested compounds were capable to induce the insulin metabolic pathway in mouse C2C12 skeletal muscle cells by remarkably stimulating both IRβ phosphorylation and 2-deoxyglucose cellular uptake.
- Ottanà, Rosaria,Maccari, Rosanna,Mortier, Jérémie,Caselli, Anna,Amuso, Simona,Camici, Guido,Rotondo, Archimede,Wolber, Gerhard,Paoli, Paolo
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supporting information
p. 112 - 127
(2014/01/06)
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- The synthesis and SAR study of phenylalanine-derived (Z)-5-arylmethylidene rhodanines as anti-methicillin-resistant Staphylococcus aureus (MRSA) compounds
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A focused library of rhodanine compounds containing novel substituents at the C5-position was synthesized and tested in vitro against a panel of clinically relevant MRSA strains. The present SAR study was based on our lead compound 1 (MIC = 1.95 μg/mL), with a focus on identifying optimal C5-arylidene substituents. In order to obtain this objective, we condensed several unique aromatic aldehydes with phenylalanine-derived rhodanine intermediates to obtain C5-substituted target rhodanine compounds for evaluation as anti-MRSA compounds. These efforts produced three compounds with significant efficacy: 23, 32 and 44, with MIC values ranging from 0.98 to 1.95 μg/mL against all tested MRSA strains as compared to the reference antibiotics penicillin G (MIC = 15.60-250.0 μg/mL) and ciprofloxacin (MIC = 7.80-62.50 μg/mL) and comparable to that of vancomycin (MIC = 0.48 μg/mL). In addition, compounds 24, 28, 37, 41, 46 and 48 (MIC = 1.95-3.90 μg/mL) were efficacious against all MRSA strains. The majority of the synthesized compounds had bactericidal activity at concentrations only two to fourfold higher than their MIC. Overall, the results suggest that compounds 23, 32 and 44 may be of potential use in the treatment of MRSA infections.
- Patel, Bhargav A.,Ashby Jr., Charles R.,Hardej, Diane,Talele, Tanaji T.
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supporting information
p. 5523 - 5527
(2013/10/01)
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- COMPOSITION FOR AGRICULTURAL USE FOR CONTROLLING OR PREVENTING PLANT DISEASES CAUSED BY PLANT PATHOGENS
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Disclosed is a composition for agricultural use, which is used for controlling or preventing plant diseases caused by plant pathogens. The composition for agricultural use contains a compound represented by formula (1), a salt thereof or a hydrate of the compound or the salt. (1) [In the formula, Z represents an oxygen atom, a sulfur atom or NRz; and E represents a furyl group, a thienyl group, a pyrrolyl group, a tetrazolyl group, a thiazolyl group, a pyrazolyl group, a phenyl group or the like.]
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Page/Page column 222-223
(2010/11/19)
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- Antimycobacterial activity of 5-arylidene derivatives of hydantoin
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The synthesis of various 5-arylidene-2-thiohydantoins and results of the primary assay in vitro for their antimycobacterial activity is reported. Eight of those compounds exhibited >90% inhibition of Mycobacterium tuberculosis growth and for them the minimum inhibitory concentrations, cytotoxicity (IC50) and the selectivity index values were determined. The most active structure, (5Z)-5-(1,1′-biphenyl-4-ylmethylene)-2-thioxoimidazolidin-4-one, showed MIC=0.78 μg/ml. For all compounds logP and logD (pH 6.5) values were calculated.
- Kiec-Kononowicz,Szymanska
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p. 909 - 916
(2007/10/03)
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