Discovery of S-phase arresting agents derived from noscapine.
Analogues of the natural product noscapine were synthesized, and their potential as antitumor agents were examined. The discovery of a novel regio- and stereoselective O-demethylation led to the synthesis of several O-alkylated analogues that induced an unexpected S-phase arrest of mammalian cells. Compound 4a was the most potent analogue inhibiting cell proliferation at an EC(50) of 1.9 microM.
Anderson
James T
JT
Athersys, Inc., 3201 Carnegie Avenue, Cleveland, Ohio 44115-2634, USA.
Ting
Anthony E
AE
Boozer
Sherry
S
Brunden
Kurt R
KR
Danzig
Joel
J
Dent
Tom
T
Harrington
John J
JJ
Murphy
Steven M
SM
Perry
Rob
R
Raber
Amy
A
Rundlett
Stephen E
SE
Wang
Jianmin
J
Wang
Nancy
N
Bennani
Youssef L
YL
D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D045744:Cell Line, Tumor; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D009665:Noscapine / Q000031:analogs & derivatives* / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D016196:S Phase / Q000187:drug effects*; D013237:Stereoisomerism; D013329:Structure-Activity Relationship
D000970:Antineoplastic Agents; D009665:Noscapine