Paenibacillus larvae is the causative agent of American foulbrood (AFB), the most serious bacterial disease affecting developing honeybee larvae and pupas. In this study, a library of 24 (thio)glycosides, glycosyl sulfones, 6-O-esters, and ethers derived from d-mannose, d-glucose, and d-galactose having C10 or C12 alkyl chain were evaluated for their antibacterial efficacy against two P. larvae strains. The efficacy of the tested compounds determined as minimal inhibitory concentrations (MICs) varied greatly. Generally, dodecyl derivatives were found to be more potent than their decylated analogs. Thioglycosides were more efficient than glycosides and sulfones. The activity of the 6-O-ether derivatives was higher than that of their ester counterparts. Seven derivatives with dodecyl chain linked (thio)glycosidically or etherically at C-6 showed high efficacy against both P. larvae strains (MICs ranged from 12.5 μM to 50 μM). Their efficacies were similar or much higher than those of selected reference compounds known to be active against P. larvae-lauric acid, monolaurin, and honeybee larval food components, 10-hydroxy-2-decenoic acid, and sebacic acid (MICs ranged from 25 μM to 6400 μM). The high efficacies of these seven derivatives suggest that they could increase the anti-P. larvae activity of larval food and improve the resistance of larvae to AFB disease through their application to honeybee colonies.

• Keywords
• 10-HDA, American foulbrood, antibacterial activity, carbohydrate (thio)ethers, carbohydrate esters, fatty acid, lauric acid, monolaurin, royal jelly,
• MeSH
• Anti-Bacterial Agents pharmacology   MeSH
• Esters pharmacology   MeSH
• Ethers pharmacology   MeSH
• Glycosides pharmacology   MeSH
• Larva MeSH
• Paenibacillus larvae * MeSH
• Paenibacillus * MeSH
• Carbohydrates pharmacology   MeSH
• Sulfides pharmacology   MeSH
• Sulfones pharmacology   MeSH
• Bees MeSH
• Animals MeSH
• Check Tag
• Animals MeSH
• Publication type
• Journal Article MeSH
• Geographicals
• United States MeSH
• Names of Substances
• Anti-Bacterial Agents MeSH
• Esters MeSH
• Ethers MeSH
• Glycosides MeSH
• Carbohydrates MeSH
• Sulfides MeSH
• Sulfones MeSH

Inhibition of the biosynthesis of complex N-glycans in the Golgi apparatus influences progress of tumor growth and metastasis. Golgi α-mannosidase II (GMII) has become a therapeutic target for drugs with anticancer activities. One critical task for successful application of GMII drugs in medical treatments is to decrease their unwanted co-inhibition of lysosomal α-mannosidase (LMan), a weakness of all known potent GMII inhibitors. A series of novel N-substituted polyhydroxypyrrolidines was synthesized and tested with modeled GH38 α-mannosidases from Drosophila melanogaster (GMIIb and LManII). The most potent structures inhibited GMIIb (Ki =50-76 μm, as determined by enzyme assays) with a significant selectivity index of IC50 (LManII)/IC50 (GMIIb) >100. These compounds also showed inhibitory activities in in vitro assays with cancer cell lines (leukemia, IC50 =92-200 μm) and low cytotoxic activities in normal fibroblast cell lines (IC50 >200 μm). In addition, they did not show any significant inhibitory activity toward GH47 Aspergillus saitoiα1,2-mannosidase. An appropriate stereo configuration of hydroxymethyl and benzyl functional groups on the pyrrolidine ring of the inhibitor may lead to an inhibitor with the required selectivity for the active site of a target α-mannosidase.

• Keywords
• Golgi α-mannosidase II, cytotoxicity, molecular modeling, pyrrolidines, swainsonine,
• MeSH
• Aspergillus enzymology   MeSH
• Cell Line MeSH
• Drosophila melanogaster enzymology   MeSH
• Nitrogen chemistry   MeSH
• Fungal Proteins antagonists & inhibitors   metabolism   MeSH
• Golgi Apparatus enzymology   MeSH
• Inhibitory Concentration 50 MeSH
• Catalytic Domain MeSH
• Humans MeSH
• Mannosidases antagonists & inhibitors   metabolism   MeSH
• Pyrrolidines chemistry   metabolism   pharmacology   MeSH
• Molecular Docking Simulation MeSH
• Binding Sites MeSH
• Cell Survival drug effects   MeSH
• Structure-Activity Relationship MeSH
• Animals MeSH
• Check Tag
• Humans MeSH
• Animals MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH
• Names of Substances
• Nitrogen MeSH
• Fungal Proteins MeSH
• Mannosidases MeSH
• mannosyl-oligosaccharide 1,3 - 1,6-alpha-mannosidase MeSH Browser
• Pyrrolidines MeSH