Speaker
Description
The phenolic phytocannabinoids frequently exhibit a prooxidant activity, however, its role in their toxic/therapeutic action remains unclear. Typically, the prooxidant character of mammalian cell cytotoxicity of hydroxybenzenes is demonstrated by a negative dependence of the cytotoxicity on the redox potential of phenoxyl radical/phenol couple (E(Ph-O•/Ph-OH) or E27 at pH 7.0). Here using quantum mechanical calculations and cyclic voltammetry, the previously unknown E27 values of 10 phytocannabinoids containing resorcinol, 1-hydroxychromene or 1-hydroxychromane moieties were estimated to be 0.72 V- 0.82 V. Using the above E27 values, it was found that the cytotoxicity of phytocannabinoids in MH22a cells follows the same two-parameter regression as that of model hydroxybenzenes, i.e., a negative dependence on E27 and a positive dependence on their octanol/water partition coefficient at pH 7.0 (log.D). The protective effects of antioxidants and the potentiating effect of carmustine evidenced the predominant prooxidant character of their cytotoxicity. In contrast, the in vitro activity of phytocannabinoids against Plasmodium falciparum FcB1 strain was much greater than that of model hydroxybenzenes. Unlike their lipophilicity-independent activity, the antiplasmodial activity of phytocannabinoids increased with their log D. This enabled to suggest that the mammalian cell cytotoxicity of phytocannabinoids may be largely determined by their induced oxidative stress, but their antiplasmodial activity may be determined by other factors.
This study was partly supported by the COST Action CA21111. We thank Alberta Melenė and Renaldas Rimkus (Sanobiotec UAB, Vilnius) for their generous gift of phytocannabinoids.