28284-05-1Relevant articles and documents
Synthesis and biological evaluation of N-naphthoyl-phenylglyoxamide-based small molecular antimicrobial peptide mimics as novel antimicrobial agents and biofilm inhibitors
Nizalapur, Shashidhar,Ho, Kitty K. K.,Kimyon, ?nder,Yee, Eugene,Berry, Thomas,Manefield, Mike,Cranfield, Charles G.,Willcox, Mark,Black, David StC,Kumar, Naresh
, p. 3623 - 3637 (2016)
Antimicrobial peptides (AMPs) are a key component of the human immune system. Synthetic AMP mimics represent a novel strategy to counteract the increasing incidence of antimicrobial resistance. Here, we describe the synthesis of novel glyoxamide derivativ
Discovery of Isatin-Based Carbohydrazones as Potential Dual Inhibitors of Fatty Acid Amide Hydrolase and Monoacylglycerol Lipase
Jaiswal, Shivani,Ayyannan, Senthil Raja
, (2021/11/09)
Using ligand-based design strategy, a set of isatin-3-carbohydrazones was designed, synthesized and evaluated for dual fatty acid amide hydrolase (FAAH) and monoacylglycerol lipase (MAGL) inhibition properties. Compound 5-chloro-N′-(5-chloro-2-oxoindolin-3-ylidene)-2-hydroxybenzohydrazide (13 b) emerged as a potent MAGL inhibitor with nanomolar activity (IC50=3.33 nM), while compound 5-chloro-N′-(1-(4-fluorobenzyl)-2-oxoindolin-3-ylidene)-2-hydroxybenzohydrazide (13 j) was the most potent selective FAAH inhibitor (IC50=37 nM). Compound 5-chloro-N′-(6-chloro-2-oxoindolin-3-ylidene)-2-hydroxybenzohydrazide (13 c) showed dual FAAH-MAGL inhibitory activity with an IC50 of 31 and 29 nM respectively. Enzyme kinetics studies revealed that the isatin-based carbohydrazones are reversible inhibitors for both FAAH and MAGL. Further, blood-brain permeability assay confirmed that the lead compounds (13 b, 13 c, 13 g, 13 m and 13 q) are suitable as CNS candidates. Molecular dynamics simulation studies revealed the putative binding modes and key interactions of lead inhibitors within the enzyme active sites. The lead dual FAAH-MAGL inhibitor 13 c showed significant antioxidant activity and neuroprotection in the cell-based cytotoxicity assay. In summary, the study yielded three potent FAAH/MAGL inhibitor compounds (13 b, 13 c and 13 j) with acceptable pharmacokinetic profile and thus can be considered as promising candidates for treating neurological and mood disorders.
Synthesis of some N-aroyl-2-oxindole benzenesulfonamide conjugates with carbonic anhydrase inhibitory activity
Awadallah, Fadi M.,Bua, Silvia,George, Riham F.,Supuran, Claudiu T.
, (2020/02/06)
Implication of carbonic anhydrases (CAs) in many physiological functions made them attractive therapeutic targets. Herein, we report the synthesis of three series of benzenesulfonamide-based compounds (5a-e, 9a-e and 10a-e) as potential ligands to four of