Taxoids are a class of successful drugs and have been successfully used in chemotherapy for a variety of cancer types. However, despite the hope and promises that these taxoids have engendered, their utility is hampered by some clinic limitations. Extensive structure-activity relationship (SAR) studies of toxoids have been performed in many different laboratories. Whereas, SAR studies that based on the new generation toxoid, larotaxel, have not been reported yet. In view of the advantages in preclinical and clinical data of larotaxel over former toxoids, new taxoids that strategicly modified at the C3'/C3'-N and C2 positions of larotaxel were designed, semi-synthesized, and examined for their potency and efficacy in vitro. As a result, it has been shown that the majority of these larotaxel analogues are exceptionally potent against both drug-sensitive tumor cells and tumor cells with drug resistance arising from P-glycoprotein over expression. Further in vivo antitumor efficacies investigations revealed A2 might be a potent antitumor drug candidate for further preclinical evaluation. (C) 2018 Elsevier Masson SAS. All rights reserved.
[1]Fudan Univ, Sch Pharm, Dept Med Chem, Shanghai 201203, Peoples R China;
[2]Pilot Natl Lab Marine Sci & Technol, Lab Marine Drugs & Biol Prod, Qingdao 266237, Peoples R China;
[3]Chinese Acad Sci, Shanghai Inst Mat Med, Div Antitumor Pharmacol, State Key Lab Drug Res, Shanghai 201203, Peoples R China;
[4]Fudan Univ, Zhangjiang Technol Inst, 825 Zhangheng Rd, Shanghai 201203, Peoples R China
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