Daptomycin is the only lipopeptide antibiotic that is widely used in clinical practice. It was di... more Daptomycin is the only lipopeptide antibiotic that is widely used in clinical practice. It was discovered by Eli Lilly and then studied and commercialized by Cubist Pharmaceuticals in 2003. Although this antibiotic has been used for 17 years, the debate over its mechanism of action is ongoing. In this paper, we discuss the different hypotheses on the mode of action of this antibiotic with a primary focus on the bacterial membrane permeabilization as the main mechanism of action. By comparing the experimental data on the oligomerization of daptomycin in membranes with properties of self-assembling cyclic peptides, we conclude that the structure of daptomycin oligomer should resemble the structures of peptide nanotubes that serve as ion channels in membranes.
Hundreds of thousands of people are dying every year in the world from infections caused by drug ... more Hundreds of thousands of people are dying every year in the world from infections caused by drug resistant bacteria. Antibiotic resistance is a rapidly increasing problem mostly as a result of the worldwide overuse and misuse of antibiotics for conditions that do not require them. The rapid spread of antibiotic resistance in bacteria makes it necessary to intensify the development of new antibiotics and new methods to combat drug resistant bacteria. The goal of this publication is to review the approaches to finding new antibiotics that are active against drug resistant bacteria. The first part of this review is focused on an analysis of the mechanisms of action of antibiotics that are used in clinical practice as well as the mechanisms of bacterial resistance. The molecular structure and modes of action of these antibiotics are reviewed with examples of detailed mechanisms of drugs interaction with the targets in bacteria. General and specific mechanisms of bacterial resistance to these antibiotics are described. Examples of new antibiotics development active against the drug resistant bacteria are presented. Full text available at http://mir-journal.org/issues/4/3/
ABSTRACT Heating of 5-phenyltetrazole with N-phenylbenzimidoyl chloride in the absence of solvent... more ABSTRACT Heating of 5-phenyltetrazole with N-phenylbenzimidoyl chloride in the absence of solvent or in toluene, dioxane, benzonitrile, pyridine or N,N-dimethylformamide results in the formation of 3,4,5-triphenyl-1,2,4-triazole 1. Thermolysis of 1-imidoyl- and 2-imidoyl-5-phenyltetrazoles (obtained from the same reagents under phase-transfer conditions) in dioxane, toluene and benzonitrile leads to 2,5-diphenyl-3H-1,3,4-benzotriazepine 2. In pyridine and N,N-dimethylformamide a mixture of triazole 1 and triazepine 2 in the ratio approximately 1:1.5 is obtained under the same conditions. Heating of imidoyltetrazoles, obtained from 5-aryltetrazoles and N-arylbenzimidoyl chlorides, in m-xylene results in formation of the corresponding 3H-1,3,4-benzotriazepines.
Daptomycin is the only lipopeptide antibiotic that is widely used in clinical practice. It was di... more Daptomycin is the only lipopeptide antibiotic that is widely used in clinical practice. It was discovered by Eli Lilly and then studied and commercialized by Cubist Pharmaceuticals in 2003. Although this antibiotic has been used for 17 years, the debate over its mechanism of action is ongoing. In this paper, we discuss the different hypotheses on the mode of action of this antibiotic with a primary focus on the bacterial membrane permeabilization as the main mechanism of action. By comparing the experimental data on the oligomerization of daptomycin in membranes with properties of self-assembling cyclic peptides, we conclude that the structure of daptomycin oligomer should resemble the structures of peptide nanotubes that serve as ion channels in membranes.
Hundreds of thousands of people are dying every year in the world from infections caused by drug ... more Hundreds of thousands of people are dying every year in the world from infections caused by drug resistant bacteria. Antibiotic resistance is a rapidly increasing problem mostly as a result of the worldwide overuse and misuse of antibiotics for conditions that do not require them. The rapid spread of antibiotic resistance in bacteria makes it necessary to intensify the development of new antibiotics and new methods to combat drug resistant bacteria. The goal of this publication is to review the approaches to finding new antibiotics that are active against drug resistant bacteria. The first part of this review is focused on an analysis of the mechanisms of action of antibiotics that are used in clinical practice as well as the mechanisms of bacterial resistance. The molecular structure and modes of action of these antibiotics are reviewed with examples of detailed mechanisms of drugs interaction with the targets in bacteria. General and specific mechanisms of bacterial resistance to these antibiotics are described. Examples of new antibiotics development active against the drug resistant bacteria are presented. Full text available at http://mir-journal.org/issues/4/3/
ABSTRACT Heating of 5-phenyltetrazole with N-phenylbenzimidoyl chloride in the absence of solvent... more ABSTRACT Heating of 5-phenyltetrazole with N-phenylbenzimidoyl chloride in the absence of solvent or in toluene, dioxane, benzonitrile, pyridine or N,N-dimethylformamide results in the formation of 3,4,5-triphenyl-1,2,4-triazole 1. Thermolysis of 1-imidoyl- and 2-imidoyl-5-phenyltetrazoles (obtained from the same reagents under phase-transfer conditions) in dioxane, toluene and benzonitrile leads to 2,5-diphenyl-3H-1,3,4-benzotriazepine 2. In pyridine and N,N-dimethylformamide a mixture of triazole 1 and triazepine 2 in the ratio approximately 1:1.5 is obtained under the same conditions. Heating of imidoyltetrazoles, obtained from 5-aryltetrazoles and N-arylbenzimidoyl chlorides, in m-xylene results in formation of the corresponding 3H-1,3,4-benzotriazepines.
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Papers by Alexander Zhivich
Full text available at http://mir-journal.org/issues/4/3/
Full text available at http://mir-journal.org/issues/4/3/