CNP-AFU (2-Chloro-4-nitrophenyl α-L-fucopyranoside)

Niclosamide

Niclosamide is not marketed in the United States. No information is available on the clinical use of niclosamide during breastfeeding. Because niclosamide is not orally absorbed it is unlikely to adversely affect the breastfed infant. No special precautions are necessary.

In vitro and in silico evaluation of N-(alkyl/aryl)-2-chloro-4-nitro-5- [(4-nitrophenyl)sulfamoyl]benzamide derivatives for antidiabetic potential using docking and molecular dynamic simulations

A series of N-(alkyl/aryl)-2-chloro-4-nitro-5-[(4-nitrophenyl)sulfamoyl]benzamide derivatives were synthesized and evaluated for its in vitro antidiabetic potential against α-glucosidase and α-amylase enzymes and also for its antimicrobial potential. Compounds N-(2-methyl-4-nitrophenyl)-2-chloro-4-nitro-5-[(4-nitrophenyl)sulfamoyl]benzamide and N-(2-methyl-5-nitrophenyl)-2-chloro-4-nitro-5-[(4-nitrophenyl)sulfamoyl]benzamide were found to be the most potent α-glucosidase and α-amylase inhibitors with IC₅₀ values of 10.13 and 1.52 ?M, respectively. The docking results depicted reasonable dock score -10.2 to -8.0 kcal/mol (α-glucosidase), -11.1 to -8.3 kcal/mol (α-amylase) and binding interactions of synthesized molecules with respective targets with enzymes. During molecular dynamic simulations, analysis of RMSD of ligand protein complex suggested stability of the most active compound at binding site of target proteins. Compound N-(2-chloro-4-nitrophenyl)-2-chloro-4-nitro-5-[(4-nitrophenyl)sulfamoyl] benzamide showed antibacterial potential against Gram positive and Gram negative bacteria and compound N-(2-methyl-5-nitrophenyl)-2-chloro-4-nitro-5-[(4-nitrophenyl)sulfamoyl] benzamide showed excellent antifungal potential against Candida albicans and Aspergillus niger. The computational studies were also executed to predict the drug-likeness and ADMET properties of the title compounds. The N-(alkyl/aryl)-2-chloro-4-nitro-5-[(4-nitrophenyl)sulfamoyl]benzamide derivatives showed significant antidiabetic and antimicrobial potential which is equally supported by the molecular dynamic and docking studies. This study will prove useful in revealing the molecular structure and receptor target site details which can be further utilized for the development of newer active antidiabetic and antimicrobial agents.

Enzymatic synthesis of 2-chloro-4-nitrophenyl 4,6-O-3-ketobutylidene beta-maltopentaoside, a substrate for alpha-amylase

A transglycosylation reaction with 2-chloro-4-nitrophenyl beta-maltoside as an acceptor was done with 4,6-O-3-ketobutylidene maltopentaose and Bacillus macerans cyclodextrin glucanotransferase in an aqueous solution containing 50% n-propanol, and there were two main transglycosylation products. They were identified as 2-chloro-4-nitrophenyl 4,6-O-3-ketobutylidene beta-maltopentaoside and 2-chloro-4-nitrophenyl 4,6-O-3-ketobutylidene beta-maltohexaoside, and their yields were 30% and 21% respectively on the basis of the decrease of 4,6-O-3-ketobutylidene maltopentaose. For the production of 2-chloro-4-nitrophenyl 4,6-O-3-ketobutylidene beta-maltopentaoside at high substrates concentrations, the addition of n-propanol in this reaction not only increased the solubility of 2-chloro-4-nitrophenyl beta-maltoside sufficiently but also suppressed side reactions.

2-Chloro-4-nitrophenyl-beta-D-maltoheptaoside: a new substrate for the determination of alpha-amylase in serum and urine

Tests for the determination of alpha-amylase activity based on oligosaccharides or their 4-nitrophenyl derivatives as substrates suffer from some disadvantages. Using a more acid indicator molecule and connecting this group in the beta-form to maltoheptaose leads to a new substrate, 2-chloro-4-nitrophenyl-beta-D-maltoheptaoside, for the determination of alpha-amylase activity. Due to its pK value, only half of the 4-nitrophenol formed from 4-nitrophenyl-alpha-D-maltoheptaoside is spectrophotometrically detectable, whereas the total product from the new substrate is responsible for a measurable absorbance. In addition the molar lineic absorbance of the product is 1.8 times higher. Thus the new test is more sensitive than those employing 4-nitrophenyl derivatives. Both P-type and S-type alpha-amylase isoenzymes have the same affinity for the new substrate; this is not the case for all the other substrates, i.e. oligosaccharides and their 4-nitrophenyl derivatives, used in alpha-amylase tests. The sample volume may be reduced, thereby removing interference by substances like bilirubin, glucose and haemoglobin. The test is insensitive to changes in temperature and pH and can be adapted to all mechanized analytical instruments.

Syntheses of modified 2-chloro-4-nitrophenyl beta-maltopentaosides as useful substrates for assay of human alpha amylase

Twenty-three novel 2-chloro-4-nitrophenyl beta-D-maltopentaosides modified at the 6(5) and/or 4(5) position were synthesized as substrates for human alpha amylase. Two human alpha amylases hydrolyzed 6(5)-deoxy-6(5)-, 6(5)-O-, and 4(5),6(5)-di-O-substituted derivatives at essentially a single D-glucosidic linkage, but 4(5),6(5)-O-bridged and 4(5)-O-substituted derivatives were hydrolyzed at two or more linkages. The amylases displayed smaller Km values for the compounds having hydrophobic modifications. In these derivatives, 2-chloro-4-nitrophenyl O-(6-bromo-6-deoxy-alpha-D-glucopyranosyl)-(1-->4)-tris[O-alpha-D- glucopyranosyl-(1-->4)]-beta-D-glucopyranoside (10), 2-chloro-4-nitrophenyl O-(6-azido-6-deoxy-alpha-D-glucopyranosyl)-(1-->4)- tris[O-alpha-D-glucopyranosyl-(1-->4)]-beta-D-glucopyranoside (19), and 2-chloro-4-nitrophenyl O-[6-O-(N-isopropyl)carbamoyl-alpha-D-glucopyranosyl]-(1-->4)- tris[O-alpha-D-glucopyranosyl-(1-->4)]-beta-D-glucopyranoside (30), which were rapidly hydrolyzed by the two amylases at a limited position at an approximately equal rate, were shown to be very useful blocked-type substrates for assay of human alpha amylase.