ABSTRACT
Cryptophycin-8 was prepared by the conversion of the epoxide group on cryptophycin-1 to a chlorohydrin. In the studies reported here, cryptophycin-8 was evaluated for preclinical activity against subcutaneous tumors of both mouse and human origin. At the highest non-toxic single course treatment, the following results were obtained (Table A). Cryptophycin-8 was less potent than cryptophycin-1 by approximately 4-fold; however, it was both more water soluble and had greater therapeutic efficacy, as demonstrated by % T/C, tumor cell log kill values, range of dose effectiveness and host cures.
Subject(s)
Antineoplastic Agents/therapeutic use , Depsipeptides , Lactams/therapeutic use , Lactones/therapeutic use , Neoplasms, Experimental/drug therapy , Animals , Antineoplastic Agents/toxicity , Drug Resistance, Multiple , Drug Resistance, Neoplasm , Humans , Lactams/toxicity , Lactones/toxicity , Lethal Dose 50 , Mice , Mice, Inbred Strains , Neoplasm Transplantation , Neoplasms, Experimental/pathologyABSTRACT
The cytotoxic sterols 1 and 2, previously isolated from Pseudobersama mossambicensis, have been synthesized in nine steps from stigmasterol, together with seven related sterols. Structure-activity relationships of these sterols in cytotoxicity and DNA-damaging assays are discussed.
