Design, Synthesis and Biological Evaluations of a Novel Series of Enediynes Constituted with DNA Cleavage, Alkylating and DNA Binding Agents via Varies Spacers

摘要

Among the three series of complicated combinatory enediynes, 3a～d were more active than 2a～c and 4a～b, in which 3a～b showed equally inhibitory activity against the growth of Hepa59T/VGH, KB and Hela with mean IC_(50) values lower than 10 μg/mL. Compounds 2a and 3b exhibited the most potent inhibitory activity against the growth of Hela cells for 4.39 μg/mL. Derivative 3d displayed the greatest ability against the growth of Hepa59T/VGH cell lines for 6.95 μg/mL, while 3a showed more cytotoxic to KB cells than other analogs. Conjugates 2a-c presented better responses than 3a-d for the DNA cleavage assay of supercoiled ΦX174.