A novel docetaxel derivative exhibiting potent anti-tumor activity and high safety in preclinical animal models.

As a taxoid agent, docetaxel (DTX) exhibits potent antitumor activity. However, severe toxic side effects and acquired multidrug resistance represent its clinical challenges. Herein, a novel docetaxel derivative (DTX-AI) is synthesized via the nucleophilic addition reaction of 4-acetylphenyl carbamate at the C10 position of the DTX framework. DTX-AI exhibits superior cytotoxicity and a higher apoptotic ratio in vitro against DTX-sensitive tumor cells (MCF-7, HeLa and A549 cells) and even DTX-resistant ones (HeLa/PTX cells), but displays less toxicity against normal cells (MRC-5 and L929 cells) compared with DTX. DTX-AI can effectively suppress the growth of HeLa-tumor xenografts in vivo and even induce complete tumor regression. Furthermore, DTX-AI shows sustained effects on the inhibition of A549-tumor xenograft growth and no obvious recurrence, even after the drug administration was stopped for 30 d. More importantly, DTX-AI has significantly reduced long-term and short-term animal toxicity and extended the survival of mice (100%) compared with DTX (0%). DTX-AI is expected to be a promising 'me-better' anti-tumor drug with higher efficiency and lower toxicity for improved chemotherapy in the clinic.