Evaluation of Cx43 Gap Junction Inhibitors Using a Quantitative Structure-Activity Relationship Model
نویسندگان
چکیده
Gap junctions (GJs) made of connexin-43 (Cx43) are necessary for the conduction electrical impulses in heart. Modulation Cx43 GJ activity may be beneficial treatment cardiac arrhythmias and other dysfunctions. The search novel GJ-modulating agents using molecular docking allows accurate prediction binding affinities ligands, which, unfortunately, often poorly correlate with their potencies. objective this study was to demonstrate that a Quantitative Structure-Activity Relationship (QSAR) model could used more precise identification potent inhibitors. Using docking, QSAR, 3D-QSAR, we evaluated 16 known inhibitors, suggested monocyclic monoterpene d-limonene as putative inhibitor, tested it experimentally HeLa cells expressing exogenous Cx43. predicted concentrations required produce 50% maximal effect (IC50) each these compounds were compared those determined (pIC50 eIC50, respectively). pIC50ies inhibitors examined by our QSAR 3D-QSAR models showed good correlation eIC50ies (R = 0.88 0.90, respectively) contrast obtained from 0.78). However, suggests inhibitor potency depend on conformation Searching new potent, selective, specific channels, propose perform primary screening model, followed validation most suitable candidates patch-clamp techniques.
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ژورنال
عنوان ژورنال: Biomedicines
سال: 2023
ISSN: ['2227-9059']
DOI: https://doi.org/10.3390/biomedicines11071972