Aminoglycoside antibiotics. XV. Chemical conversion of neomycin B to paromomycin I, 6'"-deamino-6'"-hydroxyneomycin B and 6'"-deamino-6'"-hydroxy-paromomycin I.

Pseudosaccharides containing various natural combinations of rings present in aminoglycoside antibiotics were prepared from the parent antibiotics, neomycin B, paromomycin, and lividomycin B, by oxidation of available vicinal diols and β-elimination. Pseudotrisaccharides comprising rings A, B, and C of paromomycin and lividomycin B, a pseudotrisaccharide comprising rings B, C, and D of the three antibiotics, and a 'core' pseudotrisaccharide containing rings B and C were thus prepared. These are valuable biological probes and intermediates for semisynthetic work in this series.

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ChemInform Abstract: AMINOGLYCOSIDE ANTIBIOTICS- CHEMICAL CONVERSION OF NEOMYCIN B, PAROMOMYCIN, AND LIVIDOMYCIN B INTO BIOACTIVE PSEUDOSACCHARIDES

Chemischer Informationsdienst ◽

10.1002/chin.197840332 ◽

1978 ◽

Vol 9 (40) ◽

Author(s):

S. HANESSIAN ◽

T. TAKAMOTO ◽

R. MASSE ◽

G. PATIL

Keyword(s):

Chemical Conversion ◽

Aminoglycoside Antibiotics ◽

Neomycin B

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Antibacterial Activities of Aminoglycoside Antibiotics-Derived Cationic Amphiphiles. Polyol-Modified Neomycin B-, Kanamycin A-, Amikacin-, and Neamine-Based Amphiphiles with Potent Broad Spectrum Antibacterial Activity

Journal of Medicinal Chemistry ◽

10.1021/jm1000437 ◽

2010 ◽

Vol 53 (9) ◽

pp. 3626-3631 ◽

Cited By ~ 58

Author(s):

Smritilekha Bera ◽

George G. Zhanel ◽

Frank Schweizer

Keyword(s):

Antibacterial Activity ◽

Broad Spectrum ◽

Antibacterial Activities ◽

Aminoglycoside Antibiotics ◽

Cationic Amphiphiles ◽

Neomycin B

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Influence of Linker Length and Composition on Enzymatic Activity and Ribosomal Binding of Neomycin Dimers

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.00861-15 ◽

2015 ◽

Vol 59 (7) ◽

pp. 3899-3905 ◽

Cited By ~ 16

Author(s):

Derrick Watkins ◽

Sunil Kumar ◽

Keith D. Green ◽

Dev P. Arya ◽

Sylvie Garneau-Tsodikova

Keyword(s):

Enzymatic Activity ◽

Aminoglycoside Antibiotics ◽

Substantial Decrease ◽

Selective Binding ◽

Linker Length ◽

Neomycin B ◽

A Site ◽

Site Binding

ABSTRACTThe human and bacterial A site rRNA binding as well as the aminoglycoside-modifying enzyme (AME) activity against a series of neomycin B (NEO) dimers is presented. The data indicate that by simple modifications of linker length and composition, substantial differences in rRNA selectivity and AME activity can be obtained. We tested five different AMEs with dimeric NEO dimers that were tethered via triazole, urea, and thiourea linkages. We show that triazole-linked dimers were the worst substrates for most AMEs, with those containing the longer linkers showing the largest decrease in activity. Thiourea-linked dimers that showed a decrease in activity by AMEs also showed increased bacterial A site binding, with one compound (compound 14) even showing substantially reduced human A site binding. The urea-linked dimers showed a substantial decrease in activity by AMEs when a conformationally restrictive phenyl linker was introduced. The information learned herein advances our understanding of the importance of the linker length and composition for the generation of dimeric aminoglycoside antibiotics capable of avoiding the action of AMEs and selective binding to the bacterial rRNA over binding to the human rRNA.

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