Synthesis and molecular docking studies of 4H-chromene derivatives as a calcium channel blocking agent
محورهای موضوعی : شیمی داروئیsomayeh makarem 1 , yalda kashkooli 2 , Afshin Rajabi Khorrami 3 , Shabnam nadjafi 4
1 - Department of chemistry, Karaj branch, Islamic Azad University, Karaj, Iran.
2 - 1Department of Chemistry, Karaj Branch, Islamic Azad University, Karaj, Iran
3 - Department of Chemistry, Karaj Branch, Islamic Azad University, Karaj, Iran
4 - Assistant Professor of Pharmacology, Neuroscience Research Center, Iran University of Medical Sciences, Tehran, Iran
کلید واژه: Electrosynthesis, Knoevenagel, Calcium channel blocking agents, Nimodipine, Molecular docking studies.,
چکیده مقاله :
Voltage-gated Ca2+ channels play a vital role in the transmission of electrical signals by temporarily increasing intracellular Ca2+ levels and exerting an action potential on the cell surface membrane. As a blocker of calcium channels, nimodipine specifically blocks L-type calcium channels, which are present in smooth muscle cells in blood vessels. By blocking these channels, nimodipine prevents calcium from entering the cells, resulting in relaxation and dilation of the blood vessels. In this way, several 4H-chromene derivatives were obtained through electro synthesis in propanol, using electrons as a catalyst to generate propanol anion as a base. This process involved obtaining malononitrile anion, which readily underwent Knovenagel condensation with aromatic aldehydes, followed by the reaction of the active methylene of dimedione with the electrophile C=C of the intermediate. Finally, the expected product was o−btained through cyclisation and tautomerization. The effect of current, solvent, and anode type were studied, and it was observed that the optimized current, solvent, and anode for the synthesis of nanoparticles of 4H-chromene were 50 mA/cm2, propanol, and a magnesium anode in an undivided cell at room temperature. The proposed method produces 4H-chromene directly from initial compounds in a mild and safe condition. All synthesized compounds were screened through molecular docking studies, which utilized the crystal structure of CavAb. Compound 8f exhibited the minimum binding energy and good affinity toward the active pocket of CavAb compared to nimodipine as a calcium channel blocking agent.
Voltage-gated Ca2+ channels play a vital role in the transmission of electrical signals by temporarily increasing intracellular Ca2+ levels and exerting an action potential on the cell surface membrane. As a blocker of calcium channels, nimodipine specifically blocks L-type calcium channels, which are present in smooth muscle cells in blood vessels. By blocking these channels, nimodipine prevents calcium from entering the cells, resulting in relaxation and dilation of the blood vessels. In this way, several 4H-chromene derivatives were obtained through electro synthesis in propanol, using electrons as a catalyst to generate propanol anion as a base. This process involved obtaining malononitrile anion, which readily underwent Knovenagel condensation with aromatic aldehydes, followed by the reaction of the active methylene of dimedione with the electrophile C=C of the intermediate. Finally, the expected product was o−btained through cyclisation and tautomerization. The effect of current, solvent, and anode type were studied, and it was observed that the optimized current, solvent, and anode for the synthesis of nanoparticles of 4H-chromene were 50 mA/cm2, propanol, and a magnesium anode in an undivided cell at room temperature. The proposed method produces 4H-chromene directly from initial compounds in a mild and safe condition. All synthesized compounds were screened through molecular docking studies, which utilized the crystal structure of CavAb. Compound 8f exhibited the minimum binding energy and good affinity toward the active pocket of CavAb compared to nimodipine as a calcium channel blocking agent.
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