Prediction of toxicity and pharmacological potential of selected spice compounds

Abstract

The use of computational tools in the prediction of ADME/Tox properties of compounds is growing rapidly in drug discovery as the benefits they provide in high throughput and early application in drug design are realized. Numerous examples exist of drugs that have had to be withdrawn, because of unacceptable toxicity, in clinical trials and even after reaching the market. In this study phytochemicals from selected spices were used to predict their rodent carcinogenicity, mutagenicity, PPB and BBB. Out of 108 compounds analysed, we found that only five compounds as non-mutagenic and non-carcinogenic and all the remaining were toxic in a pharmacological perspective. The five non-toxic compounds are alpha-zingiberene, delphinidin, laurotetanine, malabaricone-B and malabaricone-C. The PPB values of alpha-zingiberene, delphinidin and laurotetanine are in the <90% range (57.58, 88.41, 52.59, respectively) indicating that the three compounds were weakly bound to plasma proteins and the other two (malabaricone-B and malabaricone-C) strongly binds to plasma protein. The identification of delphinidin as a naturally occurring inhibitor of VEGF (vascular endothelial growth factor) receptors suggests that this molecule possesses important antiangiogenic properties that may be helpful for the prevention and treatment of cancer. The healing activity of malabaricone B and malabaricone C, the major antioxidant constituents of Myristaceae family, against indomethacin-induced gastric ulceration in mice has been studied. Though spices are well known for their antioxidant, antimicrobial, antinflammatory properties etc., this study clearly indicates the plethora of carcinogenic behaviour of spice compounds.