Structure‐Based Virtual Screening and Electrophysiological Evaluation of New Chemotypes of Kv1.5 Channel Blockers |
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| Authors: | Qian Yang Dr David Fedida Prof Hongjian Xu Dr Binghe Wang Prof Lupei Du Prof Xiaojian Wang Dr Minyong Li Prof Qidong You Prof |
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| Affiliation: | 1. Department of Medicinal Chemistry, China Pharmaceutical University, Nanjing, Jiangsu 210009 (China), Fax: (+86)?25‐83271351;2. Department of Anesthesiology, Pharmacology and Therapeutics, University of British Columbia, 2350 Health Sciences Mall, Vancouver, BC V6T?1Z3 (Canada);3. Department of Chemistry, Georgia State University, Atlanta, GA 30302‐4098 (USA);4. Department of Medicinal Chemistry, School of Pharmacy, Shandong University, Jinan, Shandong 250012 (China), Fax: (+86)?531‐88382076 |
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| Abstract: | Atrial fibrillation (AF) is the most prevalent nonfatal cardiac rhythm disorder associated with an increased risk of heart failure and stroke. Considering the ventricular side effects induced by anti‐arrhythmic agents in current use, Kv1.5 channel blockers have attracted a great deal of deliberation owing to their selective actions on atrial electrophysiology. Herein we report new chemotypes of Kv1.5 channel blockers that were identified through a combination of structure‐based virtual screening and in silico druglike property prediction including six scoring functions, as well as electrophysiological evaluation. Among them, five of the 18 compounds exhibited >50 % blockade ratio at 10 μM , and have structural features different from conventional Kv1.5 channel blockers. These novel scaffolds could serve as hits for further optimization and SAR studies for the discovery of selective agents to treat AF. |
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| Keywords: | atrial fibrillation consensus scoring Kv1 5 channels molecular docking virtual screening |
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