A series of 2-methylthio-1,4-dihydropyrimidine derivatives (IIa-IIl) were synthesized in good yields by alkylation of 1,2,3,4-tetrahydropyrimidines (Ia-Il) with methyl iodide in the presence of pyridine. Their structures were confirmed by elemental analysis, IR, and 1H NMR spectra. Molecular docking of title compounds was done using VLife MDS 3.5 on voltage-dependent calcium channel b subunit functional core and its complex with the a1 interaction domain i.e. AID-b complex (PDB code 1T3L) to identify potential candidates with minimum dock score for cardioprotective activity. Biological screening of the potential candidates (IIf and IIi) was done for cardioprotective activity. Adult Sprague-dawley rats were pretreated with test compounds IIf and IIi. After the treatment period, adrenaline was subcutaneously injected to rats at an interval of 24 h for 2 days to induce myocardial injury. After 48 h, rats were anaesthetized and electrocardiographic (ECG) observations were performed. Potential compounds IIf and IIi showed significant cardioprotective activity against adrenaline-induced myocardial infarction in rats. Adrenaline-induced ECG alterations such as reduced R-R interval, increased heart rate, reduced P duration, and ST-segment elevation were brought to the near normal values by pretreatment of compounds IIf and IIi.
Among the inorganic elements, selenium is one of the essential entities required in trace amounts. Selenium (Se) has a vital role to play in brain physiology. It is well demonstrated that an abnormal level of selenium is the cause of the pathogenesis of various neurodegenerative diseases. As selenium levels are age-dependent, deficiency of Se is well correlated with cognitive disability with aging which further correlates with Alzheimer’s disease. Organoselenium compounds are considered an essential therapeutic class of compounds as they have gained a wide spectrum of applications in biotransformation and are well-studied by several researchers. In recent years, a detailed analysis of the effectiveness of organoselenium compounds in attenuating disease are done. A literature search on PubMed, Embase, and Scopus databases was done using the keywords “organoselenium compounds, brain disorder, Alzheimer's, Parkinson's' disease, neurodegenerative disorders. The introduction of selenium as a functional group in aryl and heteroaryl compounds has given the lead for treating various brain ailments including Alzheimer's disease, depression, anxiety, Parkinson’s disease, etc. The organoselenium compounds are also potent antioxidants and are promising chemical entities for further studies.
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