Synthesis and cytotoxicity of 1,2-disubstituted naphth[2,3-d]imidazole-4,9-diones and related compounds.
As part of our continuing search for potential anticancer drug candidates that are selective against slowly growing solid tumors, we have synthesized several series of 1- and 2-substituted derivatives of the lead structure, 1-ethyl-2-methylnaphth[2,3-d]imidazole-4,9-dione (5). Their cytotoxic activity in the National Cancer Institute's in vitro cancer cell line panel is reported. In general, substitution of various alkyl, phenyl, or benzyl moieties did not improve activity, and compound 5 remains the most active naphth[2,3-d]imidazole-4,9-dione derivative. However, high levels of activity and selectivity were found with several related 2-(acylamino)-3-chloro-1,4-naphthoquinones (2f-j). Compound 2i, 2-[(2-fluorophenyl)acetamido]-3-chloro-1,4-naphthoquinone, has been selected for further in vivo testing and as an additional lead compound for further structural modification.
Kuo
S C
SC
Graduate Institute of Pharmaceutical Chemistry, China Medical College, Taichung, Taiwan, Republic of China.
Ibuka
T
T
Huang
L J
LJ
Lien
J C
JC
Yean
S R
SR
Huang
S C
SC
Lednicer
D
D
Morris-Natschke
S
S
Lee
K H
KH
D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D002455:Cell Division / Q000187:drug effects*; D004354:Drug Screening Assays, Antitumor; D005260:Female; D006801:Humans; D007093:Imidazoles / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D013058:Mass Spectrometry; D015394:Molecular Structure; D009285:Naphthoquinones / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D013329:Structure-Activity Relationship; D014407:Tumor Cells, Cultured
D000970:Antineoplastic Agents; D007093:Imidazoles; D009285:Naphthoquinones