Ponnusamy, Parasuraman published the artcileMolecular modeling and molecular docking studies on the derivatives of 1,4-dihydropyridine towards Cytochrome P450 for structure based drug design, Application of Dimethyl 2,6-dimethyl-4-(2-nitrophenyl)-1,4-dihydropyridine-3,5-dicarboxylate, the main research area is dihydropyridine14 cytochromeP450 cardioprotective agent cardiovascular disease.
Protein-ligand interactions are instrumental for the structure based drug design in the human health care systems to cure problematic diseases especially cardiovascular diseases. To treat the cardiovascular disease, the Calcium Channel Blockers (CCBs) such as 1,4-dihydropyridine (DHP) derivatives have been used in a effective way. In this study, the series of nine DHP derivatives (DHP I-DHP IX) have been docked in the binding pocket of Cytochrome P 450. Among these nine DHP-P 450 complexes, the DHP-III [N-(4-methoxy phenyl)-3,5 dicarbethoxy-2,6-dimethyl-4-(3-nitro phenyl)-1,4-Dihydropyridine] and DHP-VI [2,6-Dimethyl-1-phenyl-1,4-dihydro-pyridine-3,5-dicarboxylic acid di-Et ester] exhibits lowest binding energy of -11.89 and -11.14 kcal/mol resp., which indicates that these two mols. strongly bind to the binding pocket amino acid residues of P 450 when compared with the other DHP derivatives An anal. of hydrogen bonding interactions shows that Arg212 is essential for high affinity ligand binding. Subsequently, the C(8) atom in the DHPIII-P 450 complex forms strong hydrophobic interaction with Ala3l0 while the C(8) atom in the DHPVI-P 450 complex makes strong hydrogen bonding interaction with Arg212. Comparatively, the C(8) atom was not interacting with neighboring amino acids in other DHP – P 450 complexes. Further, in the DHPIII-P 450 complex, the ligand makes more hydrophobic interactions with the amino acids of Ala370, Phe304, Phe213, Ile369, Met371 and Ser119. The DHP-VI mol. forms strong hydrogen bonding interactions with P 450 whereas in the amlodipine-P 450 complex, amlodipine reduces the better chance of making hydrogen bonding interactions due to the absence of N-Ph ring. Thus the binding of two DHP derivatives such as DHP-III and DHP-VI are found to be higher and exhibit increased binding affinities towards Cytochrome P 450. These two mols. may be considered as a drug candidate for the treatment of cardio vascular diseases as well as in vivo and in vitro studies in future.
Materials Today: Proceedings published new progress about Amino acids Role: BSU (Biological Study, Unclassified), BIOL (Biological Study). 21829-25-4 belongs to class pyridine-derivatives, name is Dimethyl 2,6-dimethyl-4-(2-nitrophenyl)-1,4-dihydropyridine-3,5-dicarboxylate, and the molecular formula is C17H18N2O6, Application of Dimethyl 2,6-dimethyl-4-(2-nitrophenyl)-1,4-dihydropyridine-3,5-dicarboxylate.