61 research outputs found

    Создание пролекарств на основе антрациклиновых антибиотиков

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    Although anthracycline antibiotics are widely used in the treatment of cancer, their use is limited due to severe side-effects, including irreversible cardiotoxicity and multi-drug resistance of tumor cells. One of the promising approaches towards “ideal” anthracycline is the creation of anthracycline-based prodrugs, i.e. compounds that are less active than the parent drug (or inactive) and are converted in its active form through a metabolic process. The main goal of the development of anthracycline prodrugs is to increase the selectivity of the drug (doxorubicin or daunorubicin) towards tumor cells with simultaneous decrease in toxicity to normal cells. With this aim different types of anthracycline prodrugs were designed targeting such specific characteristics of tumor cells as lower pH and oxygenation level in comparison with normal cells, higher content of different enzymes etc. Also two-stage “enzyme-prodrug” strategies which include the selective introduction of the enzyme into the tumor cells on the first step and administration of the prodrug which is the substrate for this enzyme on the second step are developed. These strategies are classified depending on the method of “introduction” of the enzyme into tumor cells: antibody-directed enzyme prodrug therapy (ADEPT), virus-directed enzyme prodrug therapy (VDEPT) and genedirected enzyme prodrug therapy (GDEPT). The review covers recent achievements in the field of creation of different types of anthracycline prodrugsВ обзоре рассмотрены достижения последних лет в области создания пролекарств на основе антрациклиновых антибиотиков. Описаны основные принципы создания пролекарств, в том числе, различия в биологии и метаболизме опухолевых клеток, которые позволяют конструировать пролекарства, селективно расщепляющиеся в опухолевых клетках. Рассмотрены двухступенчатые стратегии «фермент-пролекарство» (ADEPT/GDEPT/VGEPT)

    Стандартные образцы состава фармацевтических субстанций противомикробных препаратов

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    The present study aims to generalize the experience of creating state reference materials (GSOs) of active substances and determine their main characteristics, standardized both in the State Pharmacopoeia of the Russian Federation and in the regulatory documents of the measurement uniformity assurance system. In connection with the violation of supply chains, the acquisition and use of foreign reference active substances became quite problematic or even impossible. As a consequence of the current difficult situation with the insufficient nomenclature of GSOs, the domestic manufacturers and developers faced urgent problems in creating them. The development of antimicrobial reference active substances will solve urgent issues of strengthening the technological sovereignty of Russia, minimize the import dependence of the Russian economy, as well as ensure the targets of the Strategy for Scientific and Technological Development of the Russian Federation to be achieved. The conclusions of the study can be applied in creating GSOs to substitute imported reference materials or surpass their level.В настоящее время в связи с нарушением цепей поставок стало довольно проблематично, а зачастую невозможно приобретение и использование стандартных образцов фармацевтических субстанций зарубежного производства. Как следствие сложившейся непростой ситуации с недостаточной номенклатурой стандартных образцов утвержденного типа (ГСО) перед производителями и разработчиками ГСО встали неотложные задачи создания таких ГСО. Разработка стандартных образцов состава фармацевтических субстанций противомикробных препаратов позволит решить насущные вопросы укрепления технологического суверенитета России, минимизировать импортозависимость отраслей российской экономики, обеспечит достижение целевых показателей Стратегии научно-технологического развития Российской Федерации. Настоящее исследование призвано обобщить опыт создания ГСО фармацевтических субстанций и определения их основных характеристик, нормируемых как в Государственной Фармакопее Российской Федерации, так и в нормативных документах системы обеспечения единства измерений. Основная значимость исследования состоит в применении приведенных в работе выводов для создания современных ГСО, способных не просто импортозаместить стандартные образцы зарубежного производства, а и временами опередить другие страны

    Creation of anthracycline prodrug

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    Although anthracycline antibiotics are widely used in the treatment of cancer, their use is limited due to severe side-effects, including irreversible cardiotoxicity and multi-drug resistance of tumor cells. One of the promising approaches towards “ideal” anthracycline is the creation of anthracycline-based prodrugs, i.e. compounds that are less active than the parent drug (or inactive) and are converted in its active form through a metabolic process. The main goal of the development of anthracycline prodrugs is to increase the selectivity of the drug (doxorubicin or daunorubicin) towards tumor cells with simultaneous decrease in toxicity to normal cells. With this aim different types of anthracycline prodrugs were designed targeting such specific characteristics of tumor cells as lower pH and oxygenation level in comparison with normal cells, higher content of different enzymes etc. Also two-stage “enzyme-prodrug” strategies which include the selective introduction of the enzyme into the tumor cells on the first step and administration of the prodrug which is the substrate for this enzyme on the second step are developed. These strategies are classified depending on the method of “introduction” of the enzyme into tumor cells: antibody-directed enzyme prodrug therapy (ADEPT), virus-directed enzyme prodrug therapy (VDEPT) and genedirected enzyme prodrug therapy (GDEPT). The review covers recent achievements in the field of creation of different types of anthracycline prodrug

    Synthesis, properties, and mechanism of action of new generation of polycyclic glycopeptide antibiotics

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    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. © 2017 Bentham Science Publishers

    Recent Trends in Synthesis of Chloramphenicol New Derivatives

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    Chloramphenicol (CAM), the bacteriostatic broad-spectrum antibiotic, isolated from Streptomyces venezuelae during the “golden era” of antibiotic discovery, nowadays has limited clinical potential due to adverse side effects and frequent antimicrobial resistance. Numerous CAM analogs were synthesized in order to find the derivatives with improved pharmacological properties and activity on resistant bacterial strains. This work aims to summarize the most recent achievements in obtaining new CAM analogs reported during the last five years. Current investigations are mainly focused on elucidating the molecular basis of the mode of CAM action and determining the mechanisms of resistance to this class of antibiotics or on studies of the possible use of the CAM scaffold to search for therapeutic agents with different CAM modes of action—such as selective antiproliferative agents or bacterial cell wall biosynthesis inhibitors. Hopefully, a deeper understanding of the CAM interactions with the target and its specificity will generate research ideas for developing new effective drugs

    Synthesis, properties, and mechanism of action of new generation of polycyclic glycopeptide antibiotics

    No full text
    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. © 2017 Bentham Science Publishers

    BUILDING AN EFFECTIVE ECONOMIC RELATIONS OF THE REPUBLIC OF CRIMEA WITH THE REGIONS OF THE RUSSIAN FEDERATION (ON EXAMPLE OF KURSK REGION)

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    This article discusses the current economic cal situation of the Crimean Republic, trends and its development potential, as well as the main problems of further development of the region. The analysis of the activities for 2015 in comparison with the previous year, put forward solutions to emerging problems, searches for ways of mutually beneficial cooperation with the Kursk region

    ECONOMIC POTENTIAL OF REPUBLIC OF CRIMEA

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    To the real article the combined economic indicators of Republic of Crimea are driven, during an analysis and research the industrial and общегеографические benefits of entry are reflected in the complement of Russian Federation, advantages are summarized from this union for every side, comparison of financial and economic position of Republic is produced to the mentioned event and on the real moment of time, the general estimation of economic potential of Crimea is reflected
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