Structure-activity relationships of epolactaene analogs as DNA polymerases inhibitors.
Epolactaene, a neuritogenic compound in human neuroblastoma cells, showed inhibitory activities against DNA polymerases alpha and beta. The synthesis and inhibitory activities of epolactaene analogs are described. The alpha,beta-epoxy-gamma-lactam moiety in the core and the length of the side chain greatly influenced the activities. Compound 5 was the strongest inhibitor of DNA polymerase alpha and beta of all synthesized compounds with IC(50) values of 13 and 78 microM, respectively. N- and O-alkyl derivatives that had modified core moieties showed moderate inhibition.
Kuramochi
Kouji
K
Frontier Research Center for Genome and Drug Discovery, Tokyo University of Science, 2641 Yamazaki, Noda, Chiba 278-8510, Japan.
Mizushina
Yoshiyuki
Y
Nagata
Seigo
S
Sugawara
Fumio
F
Sakaguchi
Kengo
K
Kobayashi
Susumu
S
D045744:Cell Line, Tumor; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D004852:Epoxy Compounds / Q000737:chemistry* / Q000494:pharmacology*; D006801:Humans; D009682:Magnetic Resonance Spectroscopy; D013058:Mass Spectrometry; D019384:Nucleic Acid Synthesis Inhibitors; D011090:Polyenes / Q000737:chemistry* / Q000494:pharmacology*; D013055:Spectrophotometry, Infrared; D013329:Structure-Activity Relationship
D004791:Enzyme Inhibitors; D004852:Epoxy Compounds; D019384:Nucleic Acid Synthesis Inhibitors; D011090:Polyenes; C095351:epolactaene