Comparative QSAR-modeling of cannabinoids-analgesics and non-steroidal anti-inflammatory drugs

Relevance. With prolonged use, non-steroidal anti-inflammatory drugs (NSAIDs) cause unwanted side effects. A possible alternative to NSAIDs can be medicines based on non-psychoactive plant cannabinoids, which have successfully proven themselves in the world market. But in the conditions of strict control over the circulation of narcotic drugs in Russian Federation, studies with cannabinoid substances are not possible. Purpose of the study. To characterize the biopharmaceutical parameters of two groups of analgesics using the quantitative structure-activity correlation (QSAR) method to demonstrate the advantages of cannabinoids over NSAIDs. Materials and methods. The objects of the study were two groups of analgesics, representatives of the class of NSAIDs and cannabinoids. QSAR method was used. Results. It was shown that the calculated Wiener (W) and Balaban (J) topological indices are in one-to-one correspondence with such biopharmaceutical parameters as equilibrium binding constants with CB1 and CB2 cannabinoid receptors, toxicity (LD50, mice/rat, per os), lipophilicity (logP). The LD50-W/J and logP-W/J diagrams clearly demonstrate that cannabinoids have higher lipophilicity and lower toxicity compared to NSAIDs. Conclusions. The results obtained open prospects for replacing NSAIDs with analgesic cannabinoid preparations and make it possible to recommend the approaches for assessing the toxicity and lipophilicity of new plant cannabinoids and their synthetic analogues.

QSAR modeling, Wiener and Balaban topological indices, cannabinoids, NSAIDs, toxicity, lipophilicity