Syntheses and evaluation of novel fatty acid-second-generation taxoid conjugates as promising anticancer agents

The syntheses and exceptional antitumor activities of a series of novel fatty acid-second-generation taxoid conjugates against human tumor xenografts are reported. Polyunsaturated fatty acids such as docosahexaenoic acid (DHA), linolenic acid, and linoleic acid were linked to the C-2′ position of the second-generation taxoids that could overcome MDR caused by overexpressed ABC transporters. The new conjugates, tested in vivo, exhibited strong activity against drug-resistant colon cancer and drug-sensitive ovarian cancer xenografts in mice. Two of the new conjugates, DHA–SB-T-1214 and DHA–SB-T-1213, were found to achieve the total regression of drug-resistant and drug-sensitive tumors, respectively, in the animal models with substantially reduced systemic toxicity.