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M. N. Preobrazhenskaya - One of the best experts on this subject based on the ideXlab platform.
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hydrophobic derivatives of Glycopeptide Antibiotics as inhibitors of protein kinases
Biochemistry, 2018Co-Authors: Giorgio Cozza, Evgenia N Olsufyeva, M Fortuna, Flavio Meggio, Stefania Sarno, M H G Kubbutat, F Totzke, C Schaechtele, Lorenzo A Pinna, M. N. PreobrazhenskayaAbstract:As key regulators of cell signaling, protein kinases (PKs) are attractive targets for therapeutic intervention in a variety of diseases. Herein, we report for the first time the inhibitory activity of polycyclic peptides, particularly, derivatives of Glycopeptide Antibiotics teicoplanin and eremomycin, against a panel of 12 recombinant human protein kinases and two protein kinases (CK1 and CK2) isolated from rat liver. Several of the investigated compounds inhibited various PKs with IC50 values below 10 μM and caused >90% suppression of the enzyme activity at 10 μM concentration. Kinetic analysis of the protein kinase CK2α inhibition by the teicoplanin aglycon analogue (7) demonstrated the non-competitive mechanism of inhibition (with regard to ATP). Interestingly, the inhibitory activity of some investigated compounds correlated with the earlier described antiviral activity against HIV, HCV, and other corona- and flaviviruses.
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inhibition of feline fipv and human sars coronavirus by semisynthetic derivatives of Glycopeptide Antibiotics
Antiviral Research, 2006Co-Authors: Jan Balzarini, Svetlana S. Printsevskaya, Evgenia N Olsufyeva, Erik De Clercq, Els Keyaerts, Leen Vijgen, Herman Egberink, Marc Van Ranst, Svetlana E Solovieva, M. N. PreobrazhenskayaAbstract:Various semisynthetic derivatives of Glycopeptide Antibiotics including vancomycin, eremomycin, teicoplanin, ristocetin A and DA-40926 have been evaluated for their inhibitory activity against feline infectious peritonitis virus (FIPV) and human (SARS-CoV, Frankfurt-1 strain) coronavirus in cell culture in comparison with their activity against human immunodeficiency virus (HIV). Several Glycopeptide derivatives modified with hydrophobic substituents showed selective antiviral activity. For the most active compounds, the 50% effective concentrations (EC50) were in the lower micromolar range. In general, removal of the carbohydrate parts of the molecules did not affect the antiviral activity of the compounds. Some compounds showed inhibitory activity against both, whereas other compounds proved inhibitory to either, FIPV or SARS-CoV. There was no close correlation between the EC50 values of the Glycopeptide derivatives for FIPV or SARS-CoV.
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polycyclic peptide and Glycopeptide Antibiotics and their derivatives as inhibitors of hiv entry
Antiviral Research, 2006Co-Authors: M. N. Preobrazhenskaya, Evgenia N OlsufyevaAbstract:Antiviral activity and other biological properties of two groups of polycyclic peptides are discussed. Antibiotics of the complestatin-kistamycin group have a structural motif similar to that of the peptide core of antibacterial Antibiotics of the vancomycin-teicoplanin group though no amino acid component in the chloropeptin-kistamicin Antibiotics is identical to an amino acid incorporated in the peptide core of the Antibiotics of the vancomycin-teicoplanin group. Chloropeptins and the hydrophobic several derivatives of antibacterial Antibiotics are inhibitors of HIV and some other viruses. They interfere with the viral (i.e. HIV) entry process. Chemical modifications of natural Glycopeptide Antibiotics led to the compounds with antiviral properties whereas antibacterial properties were lost. These Glycopeptide aglycons derivatives can be envisaged as potential lead compounds for application as microbicides against sexual HIV transmission.
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Structure-activity relationships in a series of semisynthetic polycyclic Glycopeptide Antibiotics
Russian Journal of Bioorganic Chemistry, 2006Co-Authors: E. N. Olsuf’eva, M. N. PreobrazhenskayaAbstract: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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structure activity relationship studies of a series of antiviral and antibacterial aglycon derivatives of the Glycopeptide Antibiotics vancomycin eremomycin and dechloroeremomycin
Journal of Medicinal Chemistry, 2005Co-Authors: Svetlana S. Printsevskaya, Evgenia N Olsufyeva, Elena P Mirchink, Jan Balzarini, Erik De Clercq, Svetlana E Solovieva, Elena B Isakova, M. N. PreobrazhenskayaAbstract:N-(Adamantyl-1)methyl, N-(adamantyl-2), and N-(ω-aminodecyl) amides of vancomycin, eremomycin, and dechloroeremomycin aglycons and their des-(N-Me-d-Leu) derivatives were synthesized and their antibacterial and anti-HIV activities were investigated. Carboxamides with an intact peptide core demonstrated activity against Glycopeptide-susceptible and -resistant bacteria (1−32 μM). N-(Adamantyl-1)methylcarboxamide of eremomycin aglycons had good antiretroviral activity (1.6 μM against HIV-1). Compounds with destroyed peptide core [des-(N-Me-d-Leu)-aglycon amides] were inactive against both Glycopeptide-sensitive and -resistant bacteria. (Adamantyl-1)methylamide of des-(N-Me-d-Leu)-eremomycin aglycon had good antiretroviral activity (EC50 of 5.5 μM for HIV-1 and 3.5 μM for HIV-2). (Adamantyl-1)methylamides of eremomycin aglycon and its des-(N-Me-d-Leu)-derivative are the most promising and selective antiretroviral agents. Their ability to induce bacterial resistance to Glycopeptide Antibiotics during prolonged...
Evgenia N Olsufyeva - One of the best experts on this subject based on the ideXlab platform.
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hydrophobic derivatives of Glycopeptide Antibiotics as inhibitors of protein kinases
Biochemistry, 2018Co-Authors: Giorgio Cozza, Evgenia N Olsufyeva, M Fortuna, Flavio Meggio, Stefania Sarno, M H G Kubbutat, F Totzke, C Schaechtele, Lorenzo A Pinna, M. N. PreobrazhenskayaAbstract:As key regulators of cell signaling, protein kinases (PKs) are attractive targets for therapeutic intervention in a variety of diseases. Herein, we report for the first time the inhibitory activity of polycyclic peptides, particularly, derivatives of Glycopeptide Antibiotics teicoplanin and eremomycin, against a panel of 12 recombinant human protein kinases and two protein kinases (CK1 and CK2) isolated from rat liver. Several of the investigated compounds inhibited various PKs with IC50 values below 10 μM and caused >90% suppression of the enzyme activity at 10 μM concentration. Kinetic analysis of the protein kinase CK2α inhibition by the teicoplanin aglycon analogue (7) demonstrated the non-competitive mechanism of inhibition (with regard to ATP). Interestingly, the inhibitory activity of some investigated compounds correlated with the earlier described antiviral activity against HIV, HCV, and other corona- and flaviviruses.
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Synthesis, Properties, and Mechanism of Action of New Generation of Polycyclic Glycopeptide Antibiotics.
Current Topics in Medicinal Chemistry, 2017Co-Authors: Evgenia N Olsufyeva, Anna N. TevyashovaAbstract:INTRODUCTION: The increased resistance of Glycopeptide based Antibiotics has become a serious problem for the chemotherapy of infections triggered by resistant Gram-positive bacteria. This has motivated the urgent sincere efforts to develop potent Glycopeptide-based Antibiotics in both academy and industry research laboratories. Understanding of the mechanism of action of natural and modified Glycopeptides is considered as the basis for the rational design of compounds with valuable properties to achieve the fundamental results. Several hydrophobic Glycopeptide analogues active against resistant strains were developed during the last two decades. Three drugs, namely, oritavancin, telavancin and dalbavancin were approved by FDA in 2013-2014. It was found that hydrophobic derivatives act through different mechanisms without binding with the modified target of resistant bacteria. Types: Different types of chemical modifications led to several Glycopeptide analogues active against Gram-negative bacteria as advocated by in vitro studies or demonstrating potent antiviral activity in the cell models. CONCLUSION: A new class of Glycopeptide Antibiotics with potent activity against sensitive and resistant bacterial strains has been recently reported with the aim to overcome the resistance, however, there are a lot of obscure problems in the complete understanding of their mechanisms of actions. In this review, we summarized the achievements of synthetic methods devoted to the construction of new polycyclic Glycopeptide Antibiotics and described the studies related to their mechanism of actions.
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inhibition of hepatitis c virus replication by semi synthetic derivatives of Glycopeptide Antibiotics
Journal of Antimicrobial Chemotherapy, 2011Co-Authors: Susan Obeid, Svetlana S. Printsevskaya, Evgenia N Olsufyeva, Kai Dallmeier, David Durantel, Fabien ZoulimAbstract:Objectives: Some semi-synthetic derivatives of Glycopeptide Antibiotics have been shown to exert in vitro antiviral activity against HIV and coronaviruses. Here we report and characterize the in vitro anti-hepatitis C virus (HCV) activity of several semi-synthetic derivatives of teicoplanin aglycone. Methods: Anti-HCV activity was analysed in: (i) three different subgenomic HCV replicon systems using a luciferase or quantitative RT-PCR (qRT-PCR) assay; and (ii) an infectious HCV cell culture system by means of qRT-PCR and immunofluorescence assays. Results: Several teicoplanin aglycone derivatives elicited selective anti-HCV activity in replicons as well as infectious cell culture systems, with LCTA-949 being the most potent derivative. LCTA-949 proved, in contrast to several directly acting antivirals for HCV, efficient in clearing cells of their replicons. When LCTA-949 was combined with HCV protease or polymerase inhibitors an overall additive effect was observed. Likewise, LCTA-949 was equipotent against wild-type replicons as well as against replicons resistant to polymerase and protease inhibitors. Following up to 4 months of selective pressure, no drug-resistant replicons were selected. When combined with the HCV NS3 protease inhibitor VX-950, LCTA-949 prevented the development of VX-950-resistant variants. Conclusions: Semi-synthetic derivatives of teicoplanin aglycone constitute a novel class of HCV replication inhibitors that are not cross-resistant with various HCV protease and polymerase inhibitors and in particular are potent in clearing hepatoma cells of their replicons. This class of molecules also provides a good tool to obtain novel insights into the replication cycle of HCV and into cellular factors/processes that are crucial for viral replication.
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inhibition of feline fipv and human sars coronavirus by semisynthetic derivatives of Glycopeptide Antibiotics
Antiviral Research, 2006Co-Authors: Jan Balzarini, Svetlana S. Printsevskaya, Evgenia N Olsufyeva, Erik De Clercq, Els Keyaerts, Leen Vijgen, Herman Egberink, Marc Van Ranst, Svetlana E Solovieva, M. N. PreobrazhenskayaAbstract:Various semisynthetic derivatives of Glycopeptide Antibiotics including vancomycin, eremomycin, teicoplanin, ristocetin A and DA-40926 have been evaluated for their inhibitory activity against feline infectious peritonitis virus (FIPV) and human (SARS-CoV, Frankfurt-1 strain) coronavirus in cell culture in comparison with their activity against human immunodeficiency virus (HIV). Several Glycopeptide derivatives modified with hydrophobic substituents showed selective antiviral activity. For the most active compounds, the 50% effective concentrations (EC50) were in the lower micromolar range. In general, removal of the carbohydrate parts of the molecules did not affect the antiviral activity of the compounds. Some compounds showed inhibitory activity against both, whereas other compounds proved inhibitory to either, FIPV or SARS-CoV. There was no close correlation between the EC50 values of the Glycopeptide derivatives for FIPV or SARS-CoV.
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polycyclic peptide and Glycopeptide Antibiotics and their derivatives as inhibitors of hiv entry
Antiviral Research, 2006Co-Authors: M. N. Preobrazhenskaya, Evgenia N OlsufyevaAbstract:Antiviral activity and other biological properties of two groups of polycyclic peptides are discussed. Antibiotics of the complestatin-kistamycin group have a structural motif similar to that of the peptide core of antibacterial Antibiotics of the vancomycin-teicoplanin group though no amino acid component in the chloropeptin-kistamicin Antibiotics is identical to an amino acid incorporated in the peptide core of the Antibiotics of the vancomycin-teicoplanin group. Chloropeptins and the hydrophobic several derivatives of antibacterial Antibiotics are inhibitors of HIV and some other viruses. They interfere with the viral (i.e. HIV) entry process. Chemical modifications of natural Glycopeptide Antibiotics led to the compounds with antiviral properties whereas antibacterial properties were lost. These Glycopeptide aglycons derivatives can be envisaged as potential lead compounds for application as microbicides against sexual HIV transmission.
Fabien Zoulim - One of the best experts on this subject based on the ideXlab platform.
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inhibition of hepatitis c virus replication by semi synthetic derivatives of Glycopeptide Antibiotics
Journal of Antimicrobial Chemotherapy, 2011Co-Authors: Susan Obeid, Svetlana S. Printsevskaya, Evgenia N Olsufyeva, Kai Dallmeier, David Durantel, Fabien ZoulimAbstract:Objectives: Some semi-synthetic derivatives of Glycopeptide Antibiotics have been shown to exert in vitro antiviral activity against HIV and coronaviruses. Here we report and characterize the in vitro anti-hepatitis C virus (HCV) activity of several semi-synthetic derivatives of teicoplanin aglycone. Methods: Anti-HCV activity was analysed in: (i) three different subgenomic HCV replicon systems using a luciferase or quantitative RT-PCR (qRT-PCR) assay; and (ii) an infectious HCV cell culture system by means of qRT-PCR and immunofluorescence assays. Results: Several teicoplanin aglycone derivatives elicited selective anti-HCV activity in replicons as well as infectious cell culture systems, with LCTA-949 being the most potent derivative. LCTA-949 proved, in contrast to several directly acting antivirals for HCV, efficient in clearing cells of their replicons. When LCTA-949 was combined with HCV protease or polymerase inhibitors an overall additive effect was observed. Likewise, LCTA-949 was equipotent against wild-type replicons as well as against replicons resistant to polymerase and protease inhibitors. Following up to 4 months of selective pressure, no drug-resistant replicons were selected. When combined with the HCV NS3 protease inhibitor VX-950, LCTA-949 prevented the development of VX-950-resistant variants. Conclusions: Semi-synthetic derivatives of teicoplanin aglycone constitute a novel class of HCV replication inhibitors that are not cross-resistant with various HCV protease and polymerase inhibitors and in particular are potent in clearing hepatoma cells of their replicons. This class of molecules also provides a good tool to obtain novel insights into the replication cycle of HCV and into cellular factors/processes that are crucial for viral replication.
Semra Çalangu - One of the best experts on this subject based on the ideXlab platform.
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Central venous catheter related infections: Risk factors and the effect of Glycopeptide Antibiotics
Annals of Clinical Microbiology and Antimicrobials, 2003Co-Authors: Serkan Öncü, Halit Özsüt, Ayşe Yildirim, Nahit Çakar, Haluk Eraksoy, Semra ÇalanguAbstract:Backround We undertook a prospective study of all new central venous catheters inserted into patients in the intensive care units, in order to identify the risk factors and to determine the effect of Glycopeptide Antibiotics on catheter – related infections. Methods During the study period 300 patients with central venous catheters were prospectively studied. The catheters used were nontunneled, noncuffed, triple lumen and made of polyurethane material. Catheters were cultured by semiquantitative method and blood cultures done when indicated. Data were obtained on patient age, gender, unit, primary diagnosis on admission, catheter insertion site, duration of catheterization, whether it was the first or a subsequent catheter and Glycopeptide antibiotic usage. Results Ninety-one (30.3%) of the catheters were colonized and infection was found with 50 (16.7%) catheters. Infection was diagnosed with higher rate in catheters inserted via jugular vein in comparison with subclavian vein (95% CI: 1.32–4.81, p = 0.005). The incidence of infection was higher in catheters which were kept in place for more than seven days (95% CI 1.05–3.87, p = 0.03). The incidence of infection was lower in patients who were using Glycopeptide antibiotic during catheterization (95% CI: 1.49–5.51, p = 0.005). The rate of infection with Gram positive cocci was significantly lower in Glycopeptide antibiotic using patients (p = 0.01). The most commonly isolated organism was Staphylococcus aureus (n = 52, 37.1%). Conclusion Duration of catheterization and catheter insertion site were independent risk factors for catheter related infection. Use of Glycopeptide antibiotic during catheterization seems to have protective effect against catheter related infection.
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Central venous catheter related infections: Risk factors and the effect of Glycopeptide Antibiotics
Annals of Clinical Microbiology and Antimicrobials, 2003Co-Authors: Serkan Öncü, Halit Özsüt, Ayşe Yildirim, Nahit Çakar, Haluk Eraksoy, Pinar Ay, Semra ÇalanguAbstract:Backround We undertook a prospective study of all new central venous catheters inserted into patients in the intensive care units, in order to identify the risk factors and to determine the effect of Glycopeptide Antibiotics on catheter – related infections.
Svetlana S. Printsevskaya - One of the best experts on this subject based on the ideXlab platform.
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inhibition of hepatitis c virus replication by semi synthetic derivatives of Glycopeptide Antibiotics
Journal of Antimicrobial Chemotherapy, 2011Co-Authors: Susan Obeid, Svetlana S. Printsevskaya, Evgenia N Olsufyeva, Kai Dallmeier, David Durantel, Fabien ZoulimAbstract:Objectives: Some semi-synthetic derivatives of Glycopeptide Antibiotics have been shown to exert in vitro antiviral activity against HIV and coronaviruses. Here we report and characterize the in vitro anti-hepatitis C virus (HCV) activity of several semi-synthetic derivatives of teicoplanin aglycone. Methods: Anti-HCV activity was analysed in: (i) three different subgenomic HCV replicon systems using a luciferase or quantitative RT-PCR (qRT-PCR) assay; and (ii) an infectious HCV cell culture system by means of qRT-PCR and immunofluorescence assays. Results: Several teicoplanin aglycone derivatives elicited selective anti-HCV activity in replicons as well as infectious cell culture systems, with LCTA-949 being the most potent derivative. LCTA-949 proved, in contrast to several directly acting antivirals for HCV, efficient in clearing cells of their replicons. When LCTA-949 was combined with HCV protease or polymerase inhibitors an overall additive effect was observed. Likewise, LCTA-949 was equipotent against wild-type replicons as well as against replicons resistant to polymerase and protease inhibitors. Following up to 4 months of selective pressure, no drug-resistant replicons were selected. When combined with the HCV NS3 protease inhibitor VX-950, LCTA-949 prevented the development of VX-950-resistant variants. Conclusions: Semi-synthetic derivatives of teicoplanin aglycone constitute a novel class of HCV replication inhibitors that are not cross-resistant with various HCV protease and polymerase inhibitors and in particular are potent in clearing hepatoma cells of their replicons. This class of molecules also provides a good tool to obtain novel insights into the replication cycle of HCV and into cellular factors/processes that are crucial for viral replication.
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inhibition of feline fipv and human sars coronavirus by semisynthetic derivatives of Glycopeptide Antibiotics
Antiviral Research, 2006Co-Authors: Jan Balzarini, Svetlana S. Printsevskaya, Evgenia N Olsufyeva, Erik De Clercq, Els Keyaerts, Leen Vijgen, Herman Egberink, Marc Van Ranst, Svetlana E Solovieva, M. N. PreobrazhenskayaAbstract:Various semisynthetic derivatives of Glycopeptide Antibiotics including vancomycin, eremomycin, teicoplanin, ristocetin A and DA-40926 have been evaluated for their inhibitory activity against feline infectious peritonitis virus (FIPV) and human (SARS-CoV, Frankfurt-1 strain) coronavirus in cell culture in comparison with their activity against human immunodeficiency virus (HIV). Several Glycopeptide derivatives modified with hydrophobic substituents showed selective antiviral activity. For the most active compounds, the 50% effective concentrations (EC50) were in the lower micromolar range. In general, removal of the carbohydrate parts of the molecules did not affect the antiviral activity of the compounds. Some compounds showed inhibitory activity against both, whereas other compounds proved inhibitory to either, FIPV or SARS-CoV. There was no close correlation between the EC50 values of the Glycopeptide derivatives for FIPV or SARS-CoV.
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structure activity relationship studies of a series of antiviral and antibacterial aglycon derivatives of the Glycopeptide Antibiotics vancomycin eremomycin and dechloroeremomycin
Journal of Medicinal Chemistry, 2005Co-Authors: Svetlana S. Printsevskaya, Evgenia N Olsufyeva, Elena P Mirchink, Jan Balzarini, Erik De Clercq, Svetlana E Solovieva, Elena B Isakova, M. N. PreobrazhenskayaAbstract:N-(Adamantyl-1)methyl, N-(adamantyl-2), and N-(ω-aminodecyl) amides of vancomycin, eremomycin, and dechloroeremomycin aglycons and their des-(N-Me-d-Leu) derivatives were synthesized and their antibacterial and anti-HIV activities were investigated. Carboxamides with an intact peptide core demonstrated activity against Glycopeptide-susceptible and -resistant bacteria (1−32 μM). N-(Adamantyl-1)methylcarboxamide of eremomycin aglycons had good antiretroviral activity (1.6 μM against HIV-1). Compounds with destroyed peptide core [des-(N-Me-d-Leu)-aglycon amides] were inactive against both Glycopeptide-sensitive and -resistant bacteria. (Adamantyl-1)methylamide of des-(N-Me-d-Leu)-eremomycin aglycon had good antiretroviral activity (EC50 of 5.5 μM for HIV-1 and 3.5 μM for HIV-2). (Adamantyl-1)methylamides of eremomycin aglycon and its des-(N-Me-d-Leu)-derivative are the most promising and selective antiretroviral agents. Their ability to induce bacterial resistance to Glycopeptide Antibiotics during prolonged...
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Antiretroviral Activity of Semisynthetic Derivatives of Glycopeptide Antibiotics
Journal of Medicinal Chemistry, 2003Co-Authors: Jan Balzarini, Svetlana S. Printsevskaya, Andrey Y Pavlov, M. I. Reznikova, Olga V Miroshnikova, Christophe Pannecouque, Erik De Clercq, Maria N. PreobrazhenskayaAbstract:A variety of semisynthetic derivatives of natural antibacterial Glycopeptide Antibiotics such as vancomycin, eremomycin, ristocetin A, teicoplanin A2-2, DA-40926, their aglycons, and also the products of their partial degradation with a destroyed or modified peptide core show marked anti-retroviral activity in cell culture. In particular, aglycon antibiotic derivatives containing various substituents of a preferably hydrophobic nature displayed activity against human immunodeficiency virus type 1 (HIV-1), HIV-2, and Moloney murine sarcoma virus at a 50% inhibitory concentration in the lower micromolar (1−5 μM) concentration range while not being cytostatic against human lymphocytic cells at 250 μM or higher. The mode of anti-HIV action of the antibiotic aglycon derivatives could be ascribed to inhibition of the viral entry process.
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Role of the Glycopeptide framework in the antibacterial activity of hydrophobic derivatives of Glycopeptide Antibiotics.
Journal of Medicinal Chemistry, 2003Co-Authors: Svetlana S. Printsevskaya, Andrey Y Pavlov, Evgenia N Olsufyeva, Elena P Mirchink, Maria N. PreobrazhenskayaAbstract:The antibacterial properties of Glycopeptide Antibiotics are based on their interaction with the d-Ala-d-Ala containing pentapeptide of bacterial peptidoglycan. The hydrophobic amides of vancomycin (1), teicoplanin (2), teicoplanin aglycon (3), and eremomycin (4) were compared with similar amides of minimally or low active des-(N-methyl-d-leucyl)eremomycin (5), eremomycin aglycon (6), des-(N-methyl-d-leucyl)eremomycin aglycon (7), and a teicoplanin degradation product TB-TPA (8). All hydrophobic amides of 1, 3, 4, and 6 were almost equally active against Glycopeptide-resistant enterococci (GRE) [minimum inhibitory concentrations (MIC) ≤ 4 μg/mL] and had better activity against Gram-positive strains sensitive to Glycopeptides than against GRE. Extensive degradation of the Glycopeptide framework in amides of 7 and 8 led to a decrease of anti-GRE activity (MIC = 16−64 μg/mL), and for these derivatives MIC values for bacterial strains sensitive and resistant to Glycopeptides were very close. These results sug...