identification of oridonin hybrids as potential anti-TNBC agents inducing cell cycle arrest and apoptosis by regulation of p21, γH2AX and cleaved PARP.

TNBC has been recognized as the most highly aggressive breast cancer without chemotherapeutic drugs. A collection of oridonin hybrids consisting of conventional antitumor pharmacophores including nitrogen mustards and adamantane-1-carboxylic acid were synthesized by deletion or blockade of multiple hydroxyl groups and structural rearrangement. Compound 11a showed the most promising anti-TNBC activity with nearly 15-fold more potent antiproliferative effects than oridonin against MDA-MB-231 and HCC1806.