Abstract
Spirostans (Sp) are useful in diverse therapeutical treatments, e.g., in cancer, inflammation, neurodegenerative diseases, pain, and obesity. This study aimed to design Sp as ligands for CB1 and CB2 cannabinoid receptors, which are involved in several physiological functions and diseases. SwissTargetPrediction platform was used to predict the selective biological potential of some Sp for CB1 and CB2 receptors; then, adducts were evaluated by molecular docking. The energy coupling of 155 Sp was calculated and compared to that of reference drugs. Tridimensional maps of 5TGZ (CB1) and 5ZTY (CB2) proteins were prepared and optimized from the ProteinDataBank in AutodockTools. The molecular docking was performed using Autodock Vina and redocking by means of RMSD (<1.0 Å). The Kruskal-Wallis test analyzed data to determine the influence of SP functionality on selectivity toward cannabinoid receptors. Sp interactions were compared versus reference drugs. Results provide insight into the role of specific and differential interactions of Sp and CB1/CB2 receptors. Remarkably, Sp-48 resulted positive for CB1 and Sp-114, and Sp-115 and Sp-126 for CB2 receptors. The in silico selectivity was 4.3 CB1/CB2 and 3.1 CB2/CB1, respectively. Data support the development of new CB1 and CB2 cannabinoid receptor agonists useful for preclinical studies.
Published Version
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