ABSTRACT
Five oxypropanol amine derivatives that four of them are novel have been synthesized with high yields and practical methods. in vitro antibacterial susceptibility of Acinetobacter baumannii, Pseudomonas aeruginosa, Escherichia coli and Staphylococcus aureus strains to synthesized substances were evaluated with agar well-diffusion method by comparison with commercially available drugs. Most of the bacteria were multidrug resistant. It was concluded that these compounds are much more effective than reference drugs. These eugenol bearing oxypropanolamine derivatives were also effective inhibitors against α-glycosidase, cytosolic carbonic anhydrase I and II isoforms (hCA I and II), and acetylcholinesterase (AChE) enzymes with Ki values in the range of 0.80⯱â¯0.24-3.52⯱â¯1.01⯵M for hCA I, 1.08⯱â¯0.15-3.64⯱â¯0.92⯵M for hCA II, 5.18⯱â¯0.84-12.46⯱â¯2.08⯵M for α-glycosidase, and 11.33⯱â¯2.83-32.81⯱â¯9.73⯵M for AChE, respectively.
Subject(s)
Anti-Bacterial Agents/pharmacology , Cholinergic Antagonists/pharmacology , Enzyme Inhibitors/pharmacology , Eugenol/pharmacology , Hypoglycemic Agents/pharmacology , Propanolamines/pharmacology , Acetylcholinesterase/metabolism , Acinetobacter baumannii/drug effects , Anti-Bacterial Agents/chemical synthesis , Anti-Bacterial Agents/chemistry , Carbonic Anhydrase I/antagonists & inhibitors , Carbonic Anhydrase I/metabolism , Carbonic Anhydrase II/antagonists & inhibitors , Carbonic Anhydrase II/metabolism , Cholinergic Antagonists/chemical synthesis , Cholinergic Antagonists/chemistry , Dose-Response Relationship, Drug , Enzyme Inhibitors/chemical synthesis , Enzyme Inhibitors/chemistry , Escherichia coli/drug effects , Eugenol/chemical synthesis , Eugenol/chemistry , Glycoside Hydrolases/antagonists & inhibitors , Glycoside Hydrolases/metabolism , Hypoglycemic Agents/chemical synthesis , Hypoglycemic Agents/chemistry , Microbial Sensitivity Tests , Molecular Structure , Propanolamines/chemical synthesis , Propanolamines/chemistry , Pseudomonas aeruginosa/drug effects , Staphylococcus aureus/drug effects , Structure-Activity RelationshipABSTRACT
Carbazole substituted imines (2a-l) were prepared from N-methyl-3-amino carbazole with different aldehydes. The imines compounds undergo (2+2) cycloaddition reactions with in situ ketenes to produce ß-lactam compounds (3a-l). The ß-lactam compounds were tested as inhibitors of the xanthine oxidase (XO) purified from bovine milk. The results show that these compounds exhibit inhibitory effects on XO at low concentrations with IC(50) values ranging from 21.65 to 58.04 µM. The most effective compound for XO was 4-(4-chlorophenyl)-1-(9-ethyl-9H-carbazol-3-yl)-3-phenylazetidin-2-one with IC(50) of 21.65 µM. The lactams investigated here showed effective XO inhibitory effects, in the same range as the clinically used allopurinol.
