22513-22-0Relevant academic research and scientific papers
Identification and Characterization of AES-135, a Hydroxamic Acid-Based HDAC Inhibitor That Prolongs Survival in an Orthotopic Mouse Model of Pancreatic Cancer
Shouksmith, Andrew E.,Shah, Fenil,Grimard, Michelle L.,Gawel, Justyna M.,Raouf, Yasir S.,Geletu, Mulu,Berger-Becvar, Angelika,De Araujo, Elvin D.,Luchman, H. Artee,Heaton, William L.,Bakhshinyan, David,Adile, Ashley A.,Venugopal, Chitra,O'Hare, Thomas,Deininger, Michael W.,Singh, Sheila K.,Konieczny, Stephen F.,Weiss, Samuel,Fishel, Melissa L.,Gunning, Patrick T.
, p. 2651 - 2665 (2019/03/17)
Pancreatic ductal adenocarcinoma (PDAC) is an aggressive, incurable cancer with a 20% 1 year survival rate. While standard-of-care therapy can prolong life in a small fraction of cases, PDAC is inherently resistant to current treatments, and novel therapies are urgently required. Histone deacetylase (HDAC) inhibitors are effective in killing pancreatic cancer cells in in vitro PDAC studies, and although there are a few clinical studies investigating combination therapy including HDAC inhibitors, no HDAC drug or combination therapy with an HDAC drug has been approved for the treatment of PDAC. We developed an inhibitor of HDACs, AES-135, that exhibits nanomolar inhibitory activity against HDAC3, HDAC6, and HDAC11 in biochemical assays. In a three-dimensional coculture model, AES-135 kills low-passage patient-derived tumor spheroids selectively over surrounding cancer-associated fibroblasts and has excellent pharmacokinetic properties in vivo. In an orthotopic murine model of pancreatic cancer, AES-135 prolongs survival significantly, therefore representing a candidate for further preclinical testing.
Phosphonodiamidate prodrugs of N-alkoxy analogs of a fosmidomycin surrogate as antimalarial and antitubercular agents
Courtens, Charlotte,Risseeuw, Martijn,Caljon, Guy,Cos, Paul,Martin, Anandi,Van Calenbergh, Serge
supporting information, p. 1051 - 1053 (2019/03/23)
A series of N-alkoxy analogs of a L-leucine ethyl ester phosphonodiamidate prodrug of a fosmidomycin surrogate were synthesized and investigated for their ability to inhibit in vitro growth of P. falciparum and M. tuberculosis. These compounds originate b
Acyloxybenzyl and Alkoxyalkyl Prodrugs of a Fosmidomycin Surrogate as Antimalarial and Antitubercular Agents
Courtens, Charlotte,Risseeuw, Martijn,Caljon, Guy,Cos, Paul,Van Calenbergh, Serge
, p. 986 - 989 (2018/09/25)
Two classes of prodrugs of a fosmidomycin surrogate were synthesized and investigated for their ability to inhibit in vitro growth of P. falciparum and M. tuberculosis. To this end, a novel efficient synthesis route was developed involving a cross metathe
Glycoconjugate Oxime Formation Catalyzed at Neutral pH: Mechanistic Insights and Applications of 1,4-Diaminobenzene as a Superior Catalyst for Complex Carbohydrates
?stergaard, Mads,Christensen, Niels Johan,Hjuler, Christian T.,Jensen, Knud J.,Thygesen, Mikkel B.
, p. 1219 - 1230 (2018/04/23)
The reaction of unprotected carbohydrates with aminooxy reagents to provide oximes is a key method for the construction of glycoconjugates. Aniline and derivatives serve as organocatalysts for the formation of oximes from simple aldehydes, and we have previously reported that aniline also catalyzes the formation of oximes from the more complex aldehydes, carbohydrates. Here, we present a comprehensive study of the effect of aniline analogues on the formation of carbohydrate oximes and related glycoconjugates depending on organocatalyst structure, pH, nucleophile, and carbohydrate, covering more than 150 different reaction conditions. The observed superiority of the 1,4-diaminobenzene (PDA) catalyst at neutral pH is rationalized by NMR analyses and DFT studies of reaction intermediates. Carbohydrate oxime formation at pH 7 is demonstrated by the formation of a bioactive glycoconjugate from a labile, decorated octasaccharide originating from exopolysaccharides of the soil bacterium Mesorhizobium loti. This study of glycoconjugate formation includes the first direct comparison of aniline-catalyzed reaction rates and equilibrium constants for different classes of nucleophiles, including primary oxyamines, secondary N-alkyl oxyamines, as well as aryl and arylsulfonyl hydrazides. We identified 1,4-diaminobenzene as a superior catalyst for the construction of oxime-linked glycoconjugates under mild conditions.
Structural Requirements of Histone Deacetylase Inhibitors: SAHA Analogs Modified on the Hydroxamic Acid
Bieliauskas, Anton V.,Weerasinghe, Sujith V.W.,Negmeldin, Ahmed T.,Pflum, Mary Kay H.
, p. 373 - 382 (2016/05/19)
Histone deacetylase (HDAC) proteins have emerged as targets for anti-cancer therapeutics, with several inhibitors used in the clinic, including suberoylanilide hydroxamic acid (SAHA, vorinostat). Because SAHA and many other inhibitors target all or most o
Biomimetic ferrichrome: Structural motifs for switching between narrow- and broad-spectrum activities in P. putida and E. coli
Olshvang, Evgenia,Szebesczyk, Agnieszka,Kozlowski, Henryk,Hadar, Yitzhak,Gumienna-Kontecka, Elzbieta,Shanzer, Abraham
, p. 20850 - 20858 (2015/12/11)
A series of novel ferrichrome (FC) analogs was designed based on the X-ray structure of FC in the FhuA transporter of Escherichia coli. Two strategies were employed: the first strategy optimized the overall size and relative orientation of H-bonding inter
Conformational and structural studies of N-methylacetohydroxamic acid and of its mono- and bis-chelated uranium(VI) complexes
Brandès, Stéphane,Sornosa-Ten, Alejandra,Rousselin, Yoann,Lagrelette, Mickael,Stern, Christine,Moncomble, Aurélien,Cornard, Jean-Paul,Meyer, Michel
, p. 164 - 175 (2015/12/18)
The thermodynamics and kinetics of the cis/trans isomerism of N-methylacetohydroxamic acid (NMAH) and its conjugated base (NMA-) have been reinvestigated in aqueous media by 1H NMR spectroscopy. Hindered rotation around the central C
Alkoxyamino glycoside acceptors for the regioselective synthesis of oligosaccharides using glycosynthases and transglycosidases
Teze, David,Dion, Michel,Daligault, Franck,Tran, Vinh,Andre-Miral, Corinne,Tellier, Charles
, p. 448 - 451 (2013/02/23)
Alkoxyamino derivatives of oligosaccharides have been synthesized by enzymatic synthesis using a glycosynthase and a transglycosidase. The chemoselective assembly of unprotected oligosaccharides bearing glucose at the reducing end with N-alkyl-O-benzylhydroxylamine provides sugar derivatives that are good acceptors for enzymatic synthesis using either glycosynthase or transglycosidase. Furthermore, this method affords the possibility of controlling the regioselectivity of coupling depending on the nature of the alkoxyamino substituent and provides high-yield coupling of sugars without the need for complex protecting group chemistry.
NOVEL COMPOUNDS AS RESPIRATORY STIMULANTS FOR TREATMENT OF BREATHING CONTROL DISORDERS OR DISEASES
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, (2012/06/16)
The present invention includes compositions that are useful in the treatment of breathing control diseases or disorders in a subject in need thereof. The present invention also includes a method of treating a respiratory disease or disorder in a subject in need thereof, comprising administering to the subject a therapeutically effective amount of a pharmaceutical formulation of the invention, The present invention further includes a method of preventing destabilization or stabilizing breathing rhythm in a subject in need thereof, comprising administering to the subject a therapeutically effective amount of a pharmaceutical formulation of the invention.
Syntheses and characterization of Cu2+, Ni2+ and Zn2+ binding capability of histidinehydroxamic acid derivatives
Csapó, Edit,Buglyó, Péter,Nagy, Nóra Veronika,Santos, M. Amélia,Corona, Alma,Farkas, Etelka
experimental part, p. 3137 - 3145 (2011/01/06)
Two histidinehydroxamic acid derivatives (N-methyl-histidinehydroxamic acid, N-Me-Hisha and Z-histidinehydroxamic acid, Z-Hisha) have been synthesized and their complexation with Cu2+-, Ni2+- and Zn 2+-ions has been studie
