Design, total synthesis, and evaluation of novel open-chain epothilone analogues.
[structure: see text] The design, total synthesis, and biological evaluation of two open-chain analogues of epothilone incorporating the critical C1-C8 fragment and the aromatic side chain held together by a small molecular scaffold have been achieved. Biological evaluation revealed that further restraint between the flexible C1-C8 region and the molecular scaffold may be necessary for potent inhibition of cell proliferation.
Department of Medicinal & Biological Chemistry, College of Pharmacy, University of Toledo, Toledo, Ohio 43606, USA.
Mamoun M
MM
Alhamadsheh
Richard A
RA
Hudson
L M
LM
Viranga Tillekeratne
D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D045744:Cell Line, Tumor; D004354:Drug Screening Assays, Antitumor; D034261:Epothilones / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D006801:Humans; D015394:Molecular Structure; D013237:Stereoisomerism; D013329:Structure-Activity Relationship
D000970:Antineoplastic Agents; D034261:Epothilones