RESUMEN
This review summarizes the scientific knowledge concerning the impact of vitamins, magnesium, and trace elements on various mechanisms contributing to the possible treatment and prevention of COVID-19, including its delayed consequences. A search was conducted in various databases, including PubMed, Scopus, ClinicalTrials.- gov, and Web of Science. Among the main mechanisms involved in the effects of the studied micronutrients, immune-boosting, antioxidant and anti-inflammatory effects were also highlighted. The analyzed clinical trials confirmed that supplementation with higher daily doses of some micronutrients can reduce SARS-CoV-2 viral load and hospitalization time. The potential role of most known vitamins in preventing, treating COVID-19, and rehabilitating patients was considered. The most promising agents for combating COVID-19 and its consequences might be the following vitamins: vitamin D, ascorbic acid, polyunsaturated fatty acids (PUFAs), and some B complex vitamins. Inorganic elements deserving attention include magnesium and trace elements, such as zinc, selenium, copper, and iron. Some associations were found between micronutrient deficiencies and COVID-19 severity in children, adults, and older people. Patients can obtain the aforementioned micronutrients from natural food sources or as supplements/- drugs in various dosage forms. The reviewed micronutrients might be considered adjunctive treatment strategies for COVID-19 patients.
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A series of novel 3-aryl-5H-pyrrolo[1,2-a]imidazole and 5H-imidazo[1,2-a]azepine quaternary salts were synthesized in 58-85% yields via the reaction of 3-aryl-6, 7-dihydro-5H-pyrrolo[1,2-a]imidazoles or 3-aryl-6,7,8,9-tetrahydro-5H-imidazo[1,2-a]azepines and various alkylating reagents. All compounds were characterized by 1H NMR, 13C NMR, and LC-MS. The conducted screening studies of the in vitro antimicrobial activity of the new quaternary salts derivatives established that 15 of the 18 newly synthesized compounds show antibacterial and antifungal activity. Synthesized 3-(3,4-dichlorohenyl)-1-[(4-phenoxyphenylcarbamoyl)-methyl]-6,7-dihydro-5H-pyrrolo[1,2-a]imidazol-1-ium chloride 6c possessed a broad activity spectrum towards Staphylococcus aureus, Escherichia coli, Klebsiella pneumoniae, Acinetobacter baumannii, and Cryptococcus neoformans, with a high hemolytic activity against human red blood cells and cytotoxicity against HEK-293. However, compound 6c is characterized by a low in vivo toxicity in mice (LD50 > 2000 mg/kg).
Asunto(s)
Antibacterianos/química , Antibacterianos/farmacología , Antifúngicos/química , Antifúngicos/farmacología , Imidazoles/química , Imidazoles/farmacología , Antibacterianos/síntesis química , Antifúngicos/síntesis química , Bacterias/efectos de los fármacos , Infecciones Bacterianas/tratamiento farmacológico , Hongos/efectos de los fármacos , Células HEK293 , Humanos , Imidazoles/síntesis química , Pruebas de Sensibilidad Microbiana , Micosis/tratamiento farmacológico , Sales (Química)/síntesis química , Sales (Química)/química , Sales (Química)/farmacología , Relación Estructura-ActividadRESUMEN
Simultaneous determination of drugs with different physicochemical properties necessitates thorough research and careful selection of high-performance liquid chromatography conditions. In the present study, various concepts of high-performance liquid chromatography method development for this aim have been discussed. Moreover, the work was motivated by the advantages of utilizing different chaotropic anions as a new promising approach to overcome the limitations of ion-pairing agents commonly used for this purpose. Based on log P values, atorvastatin (log P = 6.36) and lisinopril (log P = -1.22) were chosen as representative examples for lipophilic and hydrophilic drugs, respectively. Several simple, economic, fast, and reliable high-performance liquid chromatography methods were developed for their simultaneous analysis and are presented in a comparative manner, highlighting their advantages and limitations. Peak elution profile showed satisfying retentions and resolution about 3. Photo-diode array calculations were exploited for identifying the molecules by their ultra-violet spectra and peak purity, calculated and presented as rectangular-shaped ratio grams. The linearity check showed excellent results and satisfactory system suitability parameters of both peaks. This confirms the investigation results and conclusions for the influence of the chaotropic salts on N-containing molecules, by increasing their retentivities, and improving peak shapes, even on different quality columns without end-capping and base-deactivating of separation matrixes.
Asunto(s)
Cromatografía Líquida de Alta Presión/métodos , Lípidos/química , Preparaciones Farmacéuticas/análisis , Interacciones Hidrofóbicas e Hidrofílicas , Sales (Química)/químicaRESUMEN
Diuretics are the first-line therapy for widespread cardiovascular and non-cardiovascular diseases. Traditional diuretics are commonly prescribed for treatment in patients with hypertension, edema and heart failure, as well as with a number of kidney problems. They are diseases with high mortality, and the number of patients suffering from heart and kidney diseases is increasing year by year. The use of several classes of diuretics currently available for clinical use exhibits an overall favorable risk/benefit balance. However, they are not devoid of side effects. Hence, pharmaceutical researchers have been making efforts to develop new drugs with a better pharmacological profile. High-throughput screening, progress in protein structure analysis and modern methods of chemical modification have opened good possibilities for identification of new promising agents for preclinical and clinical testing. In this review, we provide an overview of the medicinal chemistry approaches toward the development of small molecule compounds showing diuretic activity that have been discovered over the past decade and are interesting drug candidates. We have discussed promising natriuretics/aquaretics/osmotic diuretics from such classes as: vasopressin receptor antagonists, SGLT2 inhibitors, urea transporters inhibitors, aquaporin antagonists, adenosine receptor antagonists, natriuretic peptide receptor agonists, ROMK inhibitors, WNK-SPAK inhibitors, and pendrin inhibitors.