Molecules, Vol. 23, Pages 2630: Structure-Based Identification of Potent Natural Product Chemotypes as Cannabinoid Receptor 1 Inverse Agonists

Molecules, Vol. 23, Pages 2630: Structure-Based Identification of Potent Natural Product Chemotypes as Cannabinoid Receptor 1 Inverse Agonists Molecules doi: 10.3390/molecules23102630 Authors: Pankaj Pandey Kuldeep K. Roy Haining Liu Guoyi Ma Sara Pettaway Walid F. Alsharif Rama S. Gadepalli John M. Rimoldi Christopher R. McCurdy Stephen J. Cutler Robert J. Doerksen Natural products are an abundant source of potential drugs, and their diversity makes them a rich and viable prospective source of bioactive cannabinoid ligands. Cannabinoid receptor 1 (CB1) antagonists are clinically established and well documented as potential therapeutics for treating obesity, obesity-related cardiometabolic disorders, pain, and drug/substance abuse, but their associated CNS-mediated adverse effects hinder the development of potential new drugs and no such drug is currently on the market. This limitation amplifies the need for new agents with reduced or no CNS-mediated side effects. We are interested in the discovery of new natural product chemotypes as CB1 antagonists, which may serve as good starting points for further optimization towards the development of CB1 therapeutics. In search of new chemotypes as CB1 antagonists, we screened the in silico purchasable natural products subset of the ZINC12 database against our reported CB1 receptor model using the structure-based virtual screening (SBVS) approach. A total of 18 out of 192 top-scoring virtual hits, selected ...
Source: Molecules - Category: Chemistry Authors: Tags: Article Source Type: research