Betulinic acid derived hydroxamates and betulin derived carbamates are interesting scaffolds for the synthesis of novel cytotoxic compounds.

The betulinic acid-derived hydroxamates 5 – 18 , the amides 19 – 24 , and betulin-derived bis-carbamates 25 – 28 as well as the carbamates 31 – 40 and 44 – 48 were prepared and evaluated for their antiproliferative activity in a photometric sulforhodamine B (SRB) assay against several human cancer cell lines and nonmalignant mouse fibroblasts (NIH 3T3). While for 3- O -acetyl hydroxamic acid 5 EC 50 values as low as EC 50 = 1.3 μM were found, N , O -bis-alkyl substituted hydroxamates showed lowered cytotoxicity (EC 50 = 16–20 μM). In general, hydroxamic acid derivatives showed only reduced selectivity for tumor cells, except for allyl substituted compound 13 (EC 50 = 5.9 μM for A2780 human ovarian carcinoma cells and EC 50 > 30 μM for nonmalignant mouse fibroblasts). The cytotoxicity of betulinic acid derived amides 19 – 24 and of betulin derived bis-carbamates 25 – 28 was low, except for N -ethyl substituted 25 . Hexyl substituted 39 showed EC 50 = 5.6 μM (518A2 cells) while for mouse fibroblasts EC 50 > 30 was determined. [ABSTRACT FROM AUTHOR]