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 1 h after injection, and most of it was metabolized from the liver in 24 h. 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.

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