In recent years, tools for the development of new drugs have been dramatically improved. These include genomic and proteomic research, numerous biophysical methods, combinatorial chemistry and screening technologies. In addition, early ADMET studies are employed in order to significantly reduce the failure rate in the development of drug candidates. As a consequence, the lead finding, lead optimization and development process has gained marked enhancement in speed and efficiency. In parallel to this development, major pharma companies are increasingly outsourcing many components of drug discovery research to biotech companies. All these measures are designed to address the need for a faster time to market. New screening methodologies have contributed significantly to the efficiency of the drug discovery process. The conventional screening of single compounds or compound libraries has been dramatically accelerated by high throughput screening methods. In addition, in silico screening methods allow the evaluation of virtual compounds. A wide range of new lead finding and lead optimization opportunities result from novel screening methods by NMR, which are the topic of this review article.

Drug Discovery Today

Quaternary ammonium-based biomedical materials: State-of-the-art, toxicological aspects and antimicrobial resistance.

The antiviral and antimicrobial activities of licorice, a widely-used Chinese herb.

Tetrazole derivatives are a prime class of heterocycles, very important to medicinal chemistry and drug design due to not only their bioisosterism to carboxylic acid and amide moieties but also to their metabolic stability and other beneficial physicochemical properties. Although more than 20 FDA-approved drugs contain 1 H- or 2 H-tetrazole substituents, their exact binding mode, structural biology, 3D conformations, and in general their chemical behavior is not fully understood. Importantly, multicomponent reaction (MCR) chemistry offers convergent access to multiple tetrazole scaffolds providing the three important elements of novelty, diversity, and complexity, yet MCR pathways to tetrazoles are far from completely explored. Here, we review the use of multicomponent reactions for the preparation of substituted tetrazole derivatives. We highlight specific applications and general trends holding therein and discuss synthetic approaches and their value by analyzing scope and limitations, and also enlighten their receptor binding mode. Finally, we estimated the prospects of further research in this field.

Tetrazoles via Multicomponent Reactions.

Properties of responsible for biological activity tetrazoles are considered. Examples are given of active pharmaceutical ingredients of modern drugs containing the tetrazole ring in the molecular structure. New publications on the synthesis and investigations of biological activity of promising tetrazole-containing compounds are cited.

Medicinal chemistry of tetrazoles

Copolymers of Sodium Styrene Sulfonate and 2-Deoxy-2-methacrylamido-D-glucose with Antiviral Activity

Implementation experience of cotton rat model for respiratory syncytial virus infection and immunopathology

Hyperactivation of the immune system remains a dramatic, life-threatening complication of viral and bacterial infections, particularly during pneumonia. Therapeutic approaches to counteract local and systemic outbreaks of cytokine storm and to prevent tissue damage remain limited. Cyclin-dependent kinases 8 and 19 (CDK8/19) potentiate transcriptional responses to the altered microenvironment, but CDK8/19 potential in immunoregulation is not fully understood. In the present study, we investigated how a selective CDK8/19 inhibitor, Senexin B, impacts the immunogenic profiles of monocytic cells stimulated using influenza virus H1N1 or bacterial lipopolysaccharides. Senexin B was able to prevent the induction of gene expression of proinflammatory cytokines in THP1 and U937 cell lines and in human peripheral blood-derived mononuclear cells. Moreover, Senexin B substantially reduced functional manifestations of inflammation, including clustering and chemokine-dependent migration of THP1 monocytes and human pulmonary fibroblasts (HPF).

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Inhibition of Cyclin-Dependent Kinases 8/19 Restricts Bacterial and Virus-Induced Inflammatory Responses in Monocytes

BACKGROUND: Respiratory syncytial infection annually affects large segments of the population around the world. Despite the ease of clinical manifestations in most adults, for children under two years of age, this disease is a serious danger, leading to the development of severe bronchiolitis, even death. 
AIM: The aim of this study was to search for drugs with antiviral activity among adamantane derivatives. 
MATERIALS AND METHODS: Preparations of the group of adamantane derivatives were synthesized in the Department of Medicinal Chemistry of Natural Compounds of the N.N. Vorozhtsov Novosibirsk Institute of Organic Chemistry SB RAS. The cytotoxicity and antiviral activity of the compounds were studied in HEp-2 cell culture using the MTT test and enzyme immunoassay, respectively. 
RESULTS: There were no drugs with high antiviral properties against RSV in this group. 
CONCLUSIONS: Despite the absence of drugs with pronounced anti-RSV properties, the information obtained in the course of the work can be used for a targeted search for antitumor substances.

Antiviral activity of adamantane derivatives against respiratory syncytial virus

1Зао Медико-биологический НПК "Цитомед", 191023, Санкт-Петербург; 2 ФГБУ "Нии гриппа" Минздрава р оссии, 197376, Санкт-Петербург Вирус гриппа является ведущей причиной инфекционной респираторной патологии человека. Способность к антигенной изменчивости и выработке лекарственной устойчивости делают актуальными поиск и разработку новых противогриппозных препаратов широкого спектра активности. В настоящей работе изучена активность комбинации глицирризиновой кислоты с дипептидом – глутамил-триптофаном (препарат орвилакс) в отношении озельтамивирустойчивого штамма вируса А/Владивосток/2/09(H1N1) на модели летальной гриппозной инфекции у белых мышей. Показано, что применение орвилакса в виде монопрепарата и комбинации с озельтамивиром приводит к снижению специфической смертности животных (индекс защиты 39–67% в зависимости от дозы вируса и сочетания препаратов), увеличению средней продолжительности жизни животных на 3,7–5 сут и снижению титров вируса в ткани легких на 1,3 lg EID50/20 мг. Соответствующие показатели для препарата сравнения тамифлю составили 8–11%, 0,5–1,5 сут и 0,6 lg EID50/20 мг. Применение орвилакса также приводило к достоверному повышению титров интерферона в крови инфицированных животных с 30,4 до 56,5 ед/мл. Полученные данные позволяют рассматривать орвилакс как перспективное противогриппозное средство, активное в отношении лекарственно-устойчивых штаммов вируса. Клю ч евые с лова: грипп; химиотерапия; глицирризиновая кислота; глутамил-триптофан; лекарственная устойчивость.

Противовирусная активность комплекса глицирризиновая кислота-глутамил-триптофан при экспериментальной летальной гриппозной инфекции у белых мышей, вызванной озельтамивирустойчивым штаммом вируса

Anna A. Shtro

Papers

Copolymers of Sodium Styrene Sulfonate and 2-Deoxy-2-methacrylamido-D-glucose with Antiviral Activity

Implementation experience of cotton rat model for respiratory syncytial virus infection and immunopathology

Inhibition of Cyclin-Dependent Kinases 8/19 Restricts Bacterial and Virus-Induced Inflammatory Responses in Monocytes

Antiviral activity of adamantane derivatives against respiratory syncytial virus