Synthesis, molecular docking, and cardioprotective activity of 2-methylthio-1,4-dihydropyrimidines

Abstract

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.

A four-component modified Biginelli reaction: A novel approach for C-2 functionalized dihydropyrimidines

“…the S-MITU formation is the first step followed by the Biginelli with the established protocol [28]. iodide which most researchers used earlier [3,16,22,24,29]. Thus, newly designed MCR also avoids the use of these toxic/expensive reagents, which are some added benefits of this novel approach.…”

Biginelli Reaction Mediated Synthesis of Antimicrobial Pyrimidine Derivatives and Their Therapeutic Properties

“…Both reactions proved to be “key methods” for the synthesis of pyridine and pyrimidine derivatives, respectively, which were greatly developed in the following period, especially due to the applications of the synthesized compounds. The Biginelli reaction has been intensively studied in the last two decades, especially due to the applications of synthesized dihydropyrimidinone compounds at the beginning, especially as calcium channel blockers of the nifedipine-type [ 4 ], and then as antitumor [ 5 , 6 , 7 , 8 ], antibacterial, antiviral [ 9 , 10 ], anti-inflammatory [ 11 , 12 ], analgesic [ 13 ], anti-Alzheimer [ 14 ], or antioxidant [ 15 ] compounds.…”

Targeting PPAR-γ to design and synthesize antidiabetic thiazolidines

“…Molecular docking is an effective tool for investigating ligand-receptor interactions and for virtual screening, which plays a key role in rational drug design (Sawant et al, 2012[ 11 ]). Here, we describe the design, synthesis, and screening of a new series of 2,4-thiazolidine derivatives using molecular docking studies with the help of VLife MDS 4.3 software.…”