In the Search For New Anticancer Drugs .28. Synthesis and Evaluation of Highly-Active Aminoxyl Labeled Amino-Acid Derivatives Containing the [N'-(2-Chloroethyl)-N'-Nitrosoamino]Carbonyl Group

WOS: A1994NX39000014PubMed ID: 7965680The aminoxyl (nitroxyl) labeled (2-chloroethyl)nitrosocarbamoyl (CNC) derivatives of amino acids, i.e., N-[[N'-(2-chloroethyl)N'-nitrosoamino] carbonyl]-A-(1-oxy-2,2,6,6-tetramethylpiperidin-4-yl)amides, A = glycyl (10a), A = L-alanyl (10b), A = L-valyl (10c), A = L-phenylalanyl (10d), were synthesized and evaluated in vitro for their anticancer activities against the murine lymphocytic leukemia P388. Compounds 10a-d possessed activities ranging from 242 to 456% increase in life span (%ILS). All CDF1 male mice treated with the highly active compounds 10b and 10c at 12 mg/kg/day for 9 days were alive after 30 days. Compounds 10a-d were then tested in vivo against the murine lymphoid leukemia L1210. Compounds 10a-d exhibited, on day 60, a %ILS of 496, 663, 663, and 581, respectively. All CDF1 male mice treated with the highly active compounds 10b and 10c at 12 mg/kg/day for 9 days were alive after 60 days. The lipophilicities of compounds 10a-d were determined using the UV method. The %ILS parameters obtained against the P388 and L1210 tumor lines were correlated with the corresponding lipophilicities, and a trend was generally observed toward an increase in cytotoxicity with a concomitant decrease in hydrophobicity