Syntheses and evaluation of novel fatty acid-second-generation taxoid conjugates as promising anticancer agents.
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.
Kuznetsova
Larissa
L
Department of Chemistry, State University of New York at Stony Brook, Stony Brook, NY 11794-3400, USA.
Chen
Jin
J
Sun
Liang
L
Wu
Xinyuan
X
Pepe
Antonella
A
Veith
Jean M
JM
Pera
Paula
P
Bernacki
Ralph J
RJ
Ojima
Iwao
I
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*
D000970:Antineoplastic Agents; D005231:Fatty Acids, Unsaturated; D043823:Taxoids