Computational Evaluation of the Druggability and Biological Activity of Iodo-1,4-dihydropyridine Derivatives

Abstract Several successful antihypertensive medicines already in clinical use are derivatives of 1,4-dihydropyridine (1,4-DHP). They are considered the most potent calcium channel blockers of which, nitro-, chloro- and fluro-1,4-DHP derivatives have been extensively investigated for biological activity [1-5]. Nevertheless, iodo-1,4-DHP derivatives have not received enough attention. Our aims were to evaluate the druglikeness and bioactivity of a new series of 2- & 3-iodophenyl-2,6-dimethyl-1,4-dihydropyridine derivatives using Molispiration software, as well as to dock these derivatives into the active domain of proteins [ion channel modulator (5KMH) and nuclear receptor ligand (5EWM)] using Molegro virtual docker. The compounds 2f, 2i, 2n, 3i and 3n were found to obey Lipinski’s rule and its extension and show good drug likeness, indicating good potential gastrointestinal permeability. Also, the bioactivity towards G protein–coupled receptors, ion channel, kinase, nuclear receptor and other enzyme targets was estimated for the tested compounds. The compounds 2c, 2h, 2m, 3c, 3h and 3m gave good docking scores especially against both ion channel modulator and nuclear receptor ligand, whereas, the other compounds had moderate bioactivities.  In conclusion, iodo-1,4-DHP derivatives give good druglikness and in silico bioactivity that justify subsequent synthesis and in vivo testing of these compounds.

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Updated: May 12, 2018 — 1:57 am