Rational drug design and synthesis of new alpha-Santonin derivatives as potential COX-2 inhibitors

Sesquiterpene compounds are widely known for their numerous pharmacological activities. Herein the focus of the authors was on alpha-Santonin, a sesquiterpene lactone from the Artemisia genus: the aim was to determine whether alpha-Santonin could be considered in the treatment of inflammation and pain. To this purpose, a small series of derivatives was designed and screened in silico against the enzyme COX-2 along with the parent compound. Drug-likeness parameters were also assessed. The compounds were eventually synthesized, and few were tested to determine their efficacy in the inhibition of COX-2 activity and expression. Overall, compound A2 was the only one with a detectable inhibitory potential of COX-2 activity whilst two of its ether derivatives demonstrated improved ability in the inhibition of COX-2 expression. (C) 2018 Elsevier Ltd. All rights reserved.