Search

Your search keyword '"David Rabuka"' showing total 2 results
Start Over Author "David Rabuka" Journal bioorganic & medicinal chemistry letters
2 results on '"David Rabuka"'

1. Structure–activity relationships of bivalent aminoglycosides and evaluation of their microbiological activities

Author

Chang-Hsing Liang, Steven J. Sucheck, David Rabuka, San-Bao Hwang, Changyong Hu, Pamela Sears, Paulo W.M. Sgarbi, Youe-Kong Shue, Kenneth Marby, Alex Romero, Sulan Yao, Yoshitaka Ichikawa, Mayling L. Cheng, and Jonathan Duffield

Subjects
Stereochemistry, medicine.drug_class, Clinical Biochemistry, Antibiotics, Drug Evaluation, Preclinical, Pharmaceutical Science, Microbial Sensitivity Tests, medicine.disease_cause, Biochemistry, Mice, Structure-Activity Relationship, chemistry.chemical_compound, Drug Discovery, medicine, Animals, Humans, Molecular Biology, Neamine, Antibacterial agent, Mice, Inbred BALB C, Chemistry, Pseudomonas aeruginosa, Organic Chemistry, Aminoglycoside, Anti-Bacterial Agents, Aminoglycosides, Staphylococcus aureus, Molecular Medicine, Female, Pharmacophore, Lead compound
Abstract

A library of 4,5- and 4,6-linked bivalent aminoglycoside (AMG) antibiotics consisting of neamine and nebramine pharmacophores have been synthesized. We probed the effect of the linker on antibiotic activity with a series of selected synthetic analogues with varied length and substituents. A number of compounds demonstrated in vitro activity against several bacterial strains and showed activity against drug resistant strains of Pseudomonas aeruginosa. Among the compounds prepared, analogues 12a–d were novel 4,6-linked AMGs containing the nebramine pharmacophore. In addition the lead compound OPT-11 possessed an ED50 of ⩽5 mg/kg in a Staphylococcus aureus ATCC 29213 mouse protection model.

Published
2005

2. Glyco-optimization of aminoglycosides: new aminoglycosides as novel anti-infective agents

Author

Yoshitaka Ichikawa, David Rabuka, San-Bao Hwang, Sulan Yao, Mayling L. Cheng, Sean M. O'Hare, Chan-Kou Hwang, Pamela Sears, Kenneth Marby, Steven J. Sucheck, Paulo W.M. Sgarbi, Changyong Hu, and Mrunali Bairi

Subjects
Glycosylation, Stereochemistry, Clinical Biochemistry, Pharmaceutical Science, Microbial Sensitivity Tests, Gram-Positive Bacteria, Biochemistry, chemistry.chemical_compound, Anti-Infective Agents, Drug Discovery, heterocyclic compounds, Sugar moiety, Molecular Biology, biology, Chemistry, Organic Chemistry, biology.organism_classification, Antimicrobial, Combinatorial chemistry, Sugar derivatives, Aminoglycosides, Drug Design, Pseudomonas aeruginosa, Molecular Medicine, Trisaccharides, Bacteria
Abstract

Glyco-optimization (OPopS TM ) of aminoglycosides has been performed by replacing the existing sugar moiety with a variety of sugar derivatives. Glycosylation of the 6-position of nebramine provided a library of novel 4,6-linked aminoglycosides (AMGs). Among them, compounds 8b , g , i , l , and 8u with 2″-amino, 2″,3″-diamino, 2″,4″-diamino, 3″,4″-diamino, 3″-amino groups, respectively, showed significant antimicrobial activity against Gram-(+) and -(−) bacteria. Several were particularly potent against Pseudomonus aeruginosa with MICs in the 1–2 μg/mL range.

Published
2004

Catalog

Books, media, physical & digital resources
See catalog results