Novel fluorinated docetaxel analog for anti-hepatoma: Molecular docking and biological evaluation

N-De-tert-butoxycarbonyl-N-[2-(1,1,1-trifluoro-2-methyl)propyloxycarbonyl]-2-debenzoyl-2-(m-fluorobenzoyl)-docetaxel (4FDT), a novel fluorinated docetaxel analog, was evaluated for its anti-hepatoma effect and possible druggability. In molecular docking studies, 4FDT coincided with paclitaxel in a part of the nucleus. In in vitro studies, 4FDT demonstrated higher anti-hepatoma activity approximately 1.5 times greater than that of docetaxel. More interestingly, 4FDT had been determined to have better Anticancer effects, even 90 times greater in patient-derived xenografts (PDX) liver Cancer cell lines than sorafenib. In the in vivo studies, 4FDT could effectively reduce the growth rate of liver Cancer H22 and HepG2 cells. Furthermore, in a preliminary study on the ex vivo distribution of 4FDT, 4FDT-IR783 was primarily concentrated in the liver 1h after injection, and most of it was metabolized from the liver in 24h. Finally, the acute toxicity test revealed fewer side effects for 4FDT (approximately 16% than docetaxel). The water solubility, which was 11 times greater than that of docetaxel, confirmed the good druggability of 4FDT. All of these results demonstrated 4FDT's great potential to be a candidate drug for liver Cancer treatment.

4FDT; Anti-hepatoma; Docetaxel; Ex vivo distribution; Patient-derived xenografts.