Influence of 2-(4-aminophenyl)benzothiazoles on growth of human ovarian carcinoma cells in vitro and in vivo.
2-(4-Aminophenyl)benzothiazole molecules substituted in the 3 position of the phenyl ring with a halogen atom or methyl moiety comprise a group of compounds that potently inhibit specific human ovarian carcinoma cell lines. GI50 values fall within the nM range. Inhibition is highly selective -- whereas the GI50 value in IGROV1 cells consistently lies at < 10 nM, SK-OV-3 presents GI50 values > 10 microM. Biphasic dose-response relationships were observed in sensitive cell lines after 48-h drug exposure. COMPARE analyses revealed the very similar profiles of anti-tumour activity of 3-substituted benzothiazoles and 5-(4-dimethylaminophenylazo)quinoline, with Pearson correlation coefficients > 0.65. Anti-tumour activity extended to preliminary in vivo tests. The growth of OVCAR-3 cells in polyvinylidene fluoride (PVDF) hollow fibres implanted in the peritoneal cavity of mice was inhibited by more than 50% after intraperitoneal (i.p.) administration of 2-(4-amino-3-methylphenyl)benzothiazole (10 mg kg(-1)), 2-(4-amino-3-chlorophenyl)benzothiazole (100 mg kg(-1)) or 2-(4-amino-3-bromophenyl)benzothiazole (150 mg kg(-1)). The growth of OVCAR-3 tumours in subcutaneously (s.c.) implanted hollow fibres was retarded by more than 50% after treatment with 2-(4-amino-3-methylphenyl)benzothiazole (6.7 and 10 mg kg(-1)). In addition, the growth of s.c. OVCAR-3 xenografts was delayed after exposure to DF 203. However, the relationship between drug concentration and growth inhibition was inverse.
Department of Pharmaceutical Sciences, University of Nottingham, UK.
T D
TD
Bradshaw
D F
DF
Shi
R J
RJ
Schultz
K D
KD
Paull
L
L
Kelland
A
A
Wilson
C
C
Garner
H H
HH
Fiebig
S
S
Wrigley
M F
MF
Stevens
D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology / Q000627:therapeutic use*; D052160:Benzothiazoles; D002455:Cell Division / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D051379:Mice; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D010051:Ovarian Neoplasms / Q000188:drug therapy*; D013844:Thiazoles / Q000494:pharmacology / Q000627:therapeutic use*; D014183:Transplantation, Heterologous; D014407:Tumor Cells, Cultured
C111133:2-(4-aminophenyl)benzothiazole; D000970:Antineoplastic Agents; D052160:Benzothiazoles; D013844:Thiazoles; C005465:benzothiazole