Structure-activity relationships in a series of semisynthetic polycyclic glycopeptide antibiotics
Identifieur interne : 001715 ( Main/Merge ); précédent : 001714; suivant : 001716Structure-activity relationships in a series of semisynthetic polycyclic glycopeptide antibiotics
Auteurs : E. N. Olsuf Va [Russie] ; M. N. Preobrazhenskaya [Russie]Source :
- Russian Journal of Bioorganic Chemistry [ 1068-1620 ] ; 2006-07-01.
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Abstract
Abstract: The main achievements in the development of methods for the design of semisynthetic antibiotics of a new generation belonging to the group of polycyclic glycopeptides directed against infections caused by multidrug-resistant bacteria and dangerous human and animal viruses are reviewed. The review is focused on the results obtained at the Gauze Institute in the area of chemical modification of natural antibiotics (eremomycin, vancomycin, teicoplanin, etc.) directed toward modification of their antibacterial and/or antiviral activity. A special emphasis is placed on the study of the mechanisms of action of these antibiotics, which could be the basis of a rational approach to their chemical modification involving the transformation of the inner binding pocket and the peripheral regions of the molecules that participate in the formation of their complexes with targets. The recently discovered antiviral activity of modified glycopeptides antibiotics is also discussed. A possibility of obtaining new highly active anti-HIV-1 and anti-HIV-2 preparations on the basis of hydrophobic derivatives of the aglycones of glycopeptide antibiotics was demonstrated. New semisynthetic derivatives of antibiotics that exhibit a high antibacterial activity in vivo, have good pharmacological characteristics, and are promising for practical use are described.
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DOI: 10.1134/S1068162006040017
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<front><div type="abstract" xml:lang="en">Abstract: The main achievements in the development of methods for the design of semisynthetic antibiotics of a new generation belonging to the group of polycyclic glycopeptides directed against infections caused by multidrug-resistant bacteria and dangerous human and animal viruses are reviewed. The review is focused on the results obtained at the Gauze Institute in the area of chemical modification of natural antibiotics (eremomycin, vancomycin, teicoplanin, etc.) directed toward modification of their antibacterial and/or antiviral activity. A special emphasis is placed on the study of the mechanisms of action of these antibiotics, which could be the basis of a rational approach to their chemical modification involving the transformation of the inner binding pocket and the peripheral regions of the molecules that participate in the formation of their complexes with targets. The recently discovered antiviral activity of modified glycopeptides antibiotics is also discussed. A possibility of obtaining new highly active anti-HIV-1 and anti-HIV-2 preparations on the basis of hydrophobic derivatives of the aglycones of glycopeptide antibiotics was demonstrated. New semisynthetic derivatives of antibiotics that exhibit a high antibacterial activity in vivo, have good pharmacological characteristics, and are promising for practical use are described.</div>
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