Synthesis, metabolism and in vitro cytotoxicity studies on novel lavendamycin antitumor agents.
A series of lavendamycin analogues with two, three or four substituents at the C-6, C-7 N, C-2', C-3' and C-11' positions were synthesized via short and efficient methods and evaluated as potential NAD(P)H:quinone oxidoreductase (NQO1)-directed antitumor agents. The compounds were prepared through Pictet-Spengler condensation of the desired 2-formylquinoline-5,8-diones with the required tryptophans followed by further needed transformations. Metabolism and toxicity studies demonstrated that the best substrates for NQO1 were also the most selectively toxic to NQO1-rich tumor cells compared to NQO1-deficient tumor cells.
Cai
Wen
W
Chemistry Department, Ball State University, Muncie, IN 47306, USA.
Hassani
Mary
M
Karki
Rajesh
R
Walter
Ervin D
ED
Koelsch
Katherine H
KH
Seradj
Hassan
H
Lineswala
Jayana P
JP
Mirzaei
Hamid
H
York
Jeremy S
JS
Olang
Fatemeh
F
Sedighi
Minoo
M
Lucas
Jennifer S
JS
Eads
Thomas J
TJ
Rose
Anthony S
AS
Charkhzarrin
Sahba
S
Hermann
Nicholas G
NG
Beall
Howard D
HD
Behforouz
Mohammad
M
D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000378:metabolism / Q000633:toxicity; D045744:Cell Line, Tumor; D006801:Humans; D016660:NAD(P)H Dehydrogenase (Quinone) / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D011994:Recombinant Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D013308:Streptonigrin / Q000031:analogs & derivatives* / Q000737:chemistry / Q000378:metabolism / Q000633:toxicity; D013329:Structure-Activity Relationship
D000970:Antineoplastic Agents; D011994:Recombinant Proteins; D013308:Streptonigrin; C034566:lavendamycin; D016660:NAD(P)H Dehydrogenase (Quinone)