Reductively activated disulfide prodrugs of paclitaxel.
A series of unsymmetrical polar disulfide prodrugs 2-5 of paclitaxel were designed and synthesized as reductively activated prodrugs. These compounds behaved as prodrugs in vitro on L2987 lung carcinoma cells. In vivo evaluation in mice demonstrated that the mutual prodrug 5 with captopril exhibited significant regressions and cures.
Vrudhula
Vivekananda M
VM
Bristol-Myers Squibb Pharmaceutical Research Institute, 5 Research Parkway, Wallingford, CT 06492, USA. vrudhula@bms.com
MacMaster
John F
JF
Li
Zhengong
Z
Kerr
David E
DE
Senter
Peter D
PD
D000818:Animals; D002455:Cell Division / Q000187:drug effects; D004220:Disulfides; D004229:Dithiothreitol / Q000494:pharmacology; D006207:Half-Life; D006801:Humans; D020128:Inhibitory Concentration 50; D051379:Mice; D008819:Mice, Nude; D009374:Neoplasms, Experimental / Q000188:drug therapy; D010084:Oxidation-Reduction; D017239:Paclitaxel; D011355:Prodrugs / Q000138:chemical synthesis / Q000378:metabolism* / Q000494:pharmacology; D016896:Treatment Outcome; D014407:Tumor Cells, Cultured
D004220:Disulfides; D011355:Prodrugs; D017239:Paclitaxel; D004229:Dithiothreitol