Selective, Nontoxic
CB<sub>2</sub> Cannabinoid <i>o</i>‑Quinone with
in Vivo Activity against Triple-Negative
Breast Cancer
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Abstract
Triple-negative breast
cancer (TNBC) represents a subtype of breast
cancer characterized by high aggressiveness. There is no current targeted
therapy for these patients whose prognosis, as a group, is very poor.
Here, we report the synthesis and evaluation of a potent antitumor
agent in vivo for this type of breast cancer designed as a combination
of quinone/cannabinoid pharmacophores. This new compound (<b>10</b>) has been selected from a series of chromenopyrazolediones with
full selectivity for the nonpsychotropic CB<sub>2</sub> cannabinoid
receptor and with efficacy in inducing death of human TNBC cell lines.
The dual concept quinone/cannabinoid was supported by the fact that
compound <b>10</b> exerts antitumor effect by inducing cell
apoptosis through activation of CB<sub>2</sub> receptors and through
oxidative stress. Notably, it did not show either cytotoxicity on
noncancerous human mammary epithelial cells nor toxic effects in vivo,
suggesting that it may be a new therapeutic tool for the management
of TNBC