Design, synthesis, and evaluation of water-soluble morpholino-decorated paclitaxel prodrugs with remarkably decreased toxicity.
Novel water-soluble paclitaxel prodrugs were designed and synthesized by introducing morpholino groups through different linkers. These derivatives showed 400-20,000-times greater water solubility than paclitaxel as well as comparable activity in MCF-7 and HeLa cell lines. The prodrug PM4 was tested in the S-180 tumor mouse model, with paclitaxel as the positive control. The results showed that PM4 had comparable antitumor activity as paclitaxel, with tumor inhibition of 54% versus 56%, and remarkably decreased toxicity. The survival rate of treated mice was 8/8 in the PM4 group, compared to 3/8 in the paclitaxel group.
['Feng|Siliang|S|', 'Chen|Kuncheng|K|', 'Wang|Chenhong|C|', 'Jiang|Xifeng|X|', 'Dong|Huajin|H|', 'Gong|Zehui|Z|', 'Liu|Keliang|K|']
D000818:Animals D000972:Antineoplastic Agents, Phytogenic D049109:Cell Proliferation D004305:Dose-Response Relationship, Drug D015195:Drug Design D004354:Drug Screening Assays, Antitumor D006367:HeLa Cells D006801:Humans D061986:MCF-7 Cells D051379:Mice D015394:Molecular Structure D060172:Morpholinos D009374:Neoplasms, Experimental D017239:Paclitaxel D011355:Prodrugs D012995:Solubility D013329:Structure-Activity Relationship D014867:Water
Paclitaxel prodrugs Morpholino group Anticancer Water-soluble derivatives