86029-44-9Relevant academic research and scientific papers
Optimization of Acetazolamide-Based Scaffold as Potent Inhibitors of Vancomycin-Resistant Enterococcus
Kaur, Jatinder,Cao, Xufeng,Abutaleb, Nader S.,Elkashif, Ahmed,Graboski, Amanda L.,Krabill, Aaron D.,Abdelkhalek, Ahmed Hassan,An, Weiwei,Bhardwaj, Atul,Seleem, Mohamed N.,Flaherty, Daniel P.
, p. 9540 - 9562 (2020/10/19)
Vancomycin-resistant enterococci (VRE) are the second leading cause of hospital-acquired infections (HAIs) attributed to a drug-resistant bacterium in the United States, and resistance to the frontline treatments is well documented. To combat VRE, we have repurposed the FDA-approved carbonic anhydrase drug acetazolamide to design potent antienterococcal agents. Through structure-activity relationship optimization we have arrived at two leads possessing improved potency against clinical VRE strains from MIC = 2 μg/mL (acetazolamide) to MIC = 0.007 μg/mL (22) and 1 μg/mL (26). Physicochemical properties were modified to design leads that have either high oral bioavailability to treat systemic infections or low intestinal permeability to treat VRE infections in the gastrointestinal tract. Our data suggest the intracellular targets for the molecules are putative α-carbonic and γ-carbonic anhydrases, and homology modeling and molecular dynamics simulations were performed. Together, this study presents potential anti-VRE therapeutic options to provide alternatives for problematic VRE infections.
CARBONIC ANHYDRASE INHIBITORS AND ANTIBIOTICS AGAINST MULTIDRUG RESISTANT BACTERIA
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Paragraph 0087; 0089; 00100, (2020/07/14)
The invention described herein generally relates to novel therapeutic compounds, and in particular to carbonic anhydrase inhibitors as a narrow spectrum antibiotics against drug resistant bacteria and methods for treating those infection diseases in mammals using the described carbonic anhydrase inhibitors or a pharmaceutical formulation thereof.
Acetazolamide-based fungal chitinase inhibitors
Schüttelkopf, Alexander W.,Gros, Ludovic,Blair, David E.,Frearson, Julie A.,Van Aalten, Daan M.F.,Gilbert, Ian H.
experimental part, p. 8334 - 8340 (2011/02/28)
Chitin is an essential structural component of the fungal cell wall. Chitinases are thought to be important for fungal cell wall remodelling, and inhibition of these enzymes has been proposed as a potential strategy for development of novel anti-fungals. The fungal pathogen Aspergillus fumigatus possesses two distinct multi-gene chitinase families. Here we explore acetazolamide as a chemical scaffold for the inhibition of an A. fumigatus 'plant-type' chitinase. A co-crystal structure of AfChiA1 with acetazolamide was used to guide synthesis and screening of acetazolamide analogues that yielded SAR in agreement with these structural data. Although acetazolamide and its analogues are weak inhibitors of the enzyme, they have a high ligand efficiency and as such are interesting leads for future inhibitor development.
Treatment of chronic inflammatory joint disease with arylsulfonamides
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, (2008/06/13)
A method of treating chronic inflammatory joint disease with arylsulfonamides of the formula: wherein R1 and R2 are selected from hydrogen, lower alkyl, lower alkenyl, cycloalkyl, phenyl, loweralkylphenyl, 2 or 3 pyrrolidinyl, 2 or 3-(N-loweralkylpyrrolidinyl, or R1 and R2 taken together may form pyrrolidinyl or piperidinyl heterocyclic amino radicals and Z is an aryl group selected from substituted or unsubstituted tetrazole, 1,3,4-thiadiazole, 1,2,4-triazole, benzothiazole, benzimidazole, imidazole, pyridyl, 4,6-dimethyl pyrimidine, benzene or naphthalene is disclosed.
