This review considers issues dealing with the role of nitric oxide and endothelial function/dysfunction in providing a number of physiological and pathophysiological processes and various body systems functioning. It also covers in details the possible ways of pharmacological management of endothelial dysfunction (ED) using drugs of different pharmacological groups (classes). Diverse pharmacological effects which have various degree of intensity and presented at various stages of ED pathogenesis are discussed. The value and urgency of search and development of agents with endothelial protection potential are studied in available experimental and clinical works on the considerable role of endothelial system in cardiovascular diseases and lack of specific means for prevention and treatment of endothelial dysfunction. Integrated morphological-functional approach to assessment of ED and endothelial protection of substances was developed and implemented in experimental practice in Cardiovascular Agents Laboratory of the Volgograd State Medical University Research Institute of Pharmacology. Various ED models were tested and most valid ones were selected. Еndothelial protection of new compounds such as Salifen and Flavicin are considered and compared with cardiovascular drugs, antioxidants with metabolic effects, GABA derivatives. These drugs are assumed to belong to a new class of drugs – endothelial protection drugs.

Выявлено, что замена питьевой воды на 1,8 % раствор NaCl у самок-крыс в период гестации вызывает экспериментальную преэклампсию (ЭП), о чем свидетельствует повышение артериального давления, протеинурия и появление отеков у животных контрольной группы по сравнению с беременными самками с обычным питьевым режимом. У животных с ЭП наблюдается нарушение вазодилатирующей функции эндотелия, микроциркуляции, повышение коагуляционного и тромбогенного потенциалов крови, активируются процессы перекисного окисления липидов (ПОЛ) на фоне снижения активности ферментов антиоксидантной защиты. Введение фенибута самкам с ЭП в дозе 25 мг/кг ежедневно перорально в течение беременности предотвращает повышение АД, степень выраженности протеинурии и отеков. Фенибут улучшает вазодилатирующую и антитромботическую функцию эндотелия, способствует увеличению маточного кровотока и микроциркуляции, ограничению процессов ПОЛ и повышению активности ферментов антиоксидантной системы.

Quinazolin-4(3H)-one derivatives exhibiting a wide spectrum of a pharmacological activity, represent a promising class of substances used to obtain antibacterial agents, which is especially important in the context of the emergence of pathogenic microorganisms’ resistance to drugs used in medicine. It has been proved that compounds having a naphthyl radical in the molecule, as well as an amide group bound to the benzene ring as quinazolinone substituents, are characterized by a pronounced antimicrobial activity against Staphylococcus aureus and Streptococcus pneumoniae.The aim of the research is a primary microbiological screening of the in vitro antimicrobial activity of new quinazolin-4(3H)-one derivatives against Staphylococcus aureus and Streptococcus pneumoniae, as well as the assessment of the relationship between the pharmacological effect and the structural transformation of the substance molecule, lipophilicity and the possibility of forming resistance to them.Materials and methods. The experimental studies have been carried out using well-known nosocomial pathogens of infectious and inflammatory diseases Staphylococcus aureus and Streptococcus pneumoniae by a serial dilution method.Results. A compound containing a naphthyl radical in its structure, which contributes to an increase in the hydrophobicity of the substance and its solubility in the membrane of a bacterial cell, has a bacteriostatic effect against both Staphylococcus aureus and Streptococcus pneumoniae. A similar pharmacological effect is exhibited by a derivative with an amide group as a substituent of the quinazolinone nucleus linked to a phenyl radical, which probably contributes to an increase in the degree of binding to active sites of enzymes involved in the DNA replication, and protein synthesis. Obviously, the increased lipophilicity, which promotes better binding to the efflux protein, cannot serve as objective characteristics of the emergence possibility of the pathogen’s resistance to this substance.Conclusion. Among the synthesized compounds, the leading substances that exhibit an antimicrobial activity against Staphylococcus aureus and Streptococcus pneumonia, have been identified. The assessment of the chemical structure made it possible to substantiate their pharmacological action and draw conclusions about the possibility of developing resistance to it in microbial cells.

Синтезированы новые конденсированные пиримидиновые соединения, имеющие бензаннелированную хиназолиновую структуру с различными функциональными заместителями в положении N3 пиримидиновой системы: 2-метил-3-(2-фенил-2-оксоэтил)хиназолин-4(3H)-он; 3-(2-трет-бутил-2-оксоэтил)хиназолин-4(3H)-он; 3-[2-(1-нафтил)-2-оксоэтил]-6-бромхиназолин-4(3H)-он; 3-(2-изопропилокси-2-оксоэтил)хиназолин-4(3H)-он; 3-[2-[(4,6-диметилпиримидин-2-ил)амино]-2-оксоэтил]хиназолин-4(3H)-он. Установлено, что новые производные хиназолина оказывают корригирующее влияние на процессы пролиферации в иммунокомпетентных органах, восстанавливая количество спленоцитов и тимоцитов на фоне циклофосфановой иммунодепрессии у мышей линии СВА обоего пола 3 – 4-месячного возраста.