title: Syntheses and evaluation of novel fatty acid-second-generation taxoid conjugates as promising anticancer agents.
abstract: 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.
authors.affiliation: Department of Chemistry, State University of New York at Stony Brook, Stony Brook, NY 11794-3400, USA.
authors.forename: Larissa
authors.initials: L
authors.lastname: Kuznetsova
authors.forename: Jin
authors.initials: J
authors.lastname: Chen
authors.forename: Liang
authors.initials: L
authors.lastname: Sun
authors.forename: Xinyuan
authors.initials: X
authors.lastname: Wu
authors.forename: Antonella
authors.initials: A
authors.lastname: Pepe
authors.forename: Jean M
authors.initials: JM
authors.lastname: Veith
authors.forename: Paula
authors.initials: P
authors.lastname: Pera
authors.forename: Ralph J
authors.initials: RJ
authors.lastname: Bernacki
authors.forename: Iwao
authors.initials: I
authors.lastname: Ojima
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D004354:Drug Screening Assays, Antitumor; D005231:Fatty Acids, Unsaturated / Q000737:chemistry*; D006801:Humans; D008968:Molecular Conformation; D013329:Structure-Activity Relationship; D043823:Taxoids / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*
chemical_list: D000970:Antineoplastic Agents; D005231:Fatty Acids, Unsaturated; D043823:Taxoids