Influence of 2-(4-aminophenyl)benzothiazoles on growth of human ovarian carcinoma cells in vitro and in vivo

Abstract

Summary 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. G150 values fall within the nm range. Inhibition is highly selective -whereas the G150 value in IGROV1 cells consistently lies at < 10 nM, SK-OV-3 presents G150 values > 10jIM. 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

Mechanisms of acquired resistance to 2-(4-aminophenyl)benzothiazole (CJM 126, NSC 34445)

“…Acquired resistance to CJM 126 conferred cross-resistance to 3′ substituted analogues (Table 1). In the NCI COMPARE program Pearson Correlation Coefficients above 0.7 were observed only between 2-(4-aminophenyl)benzothiazole analogues (Bradshaw et al, 1998b). Such observations indicate shared mechanisms of action.…”

Synthesis and antitumor activity evaluation of new 2-(4-aminophenyl)benzothiazole derivatives bearing different heterocyclic rings

“…Compounds 3,6,8,10,11,12,16,18 and 20 were selected by NCI for 60 human tumor cell lines' anticancer screening test at single dose assay. In vitro single-dose anticancer assay was performed in full NCI 60 cell panel representing L, NSCLC, CC, CNSC, M, OC, RC, PC, and BC.…”

“…Unexpectedly, it was found that, 2-(4-aminophenyl)benzothiazole derivatives inhibit cancer cell growth with nanomolar scale against a large panel of human cancer cell lines particularly against breast, colon and ovarian cell lines in in vitro anticancer screening program of the National Cancer Institute (NCI) with a characteristic biphasic doseresponse relationship 6,7 . Up to present, scientists Shi and Bradshaw have a series of studies on antitumor activity of some benzothiazole derivatives [8][9][10][11][12][13][14] . First, the original lead compound 2-(4-aminophenyl)benzothiazole (CJM 126, NSC34445), which was originally prepared as a synthetic intermediate in a program of screening for tyrosine-kinase inhibitors, was found to possess selective in vitro activity against MCF-7 breast carcinoma cell line.…”

“…First, the original lead compound 2-(4-aminophenyl)benzothiazole (CJM 126, NSC34445), which was originally prepared as a synthetic intermediate in a program of screening for tyrosine-kinase inhibitors, was found to possess selective in vitro activity against MCF-7 breast carcinoma cell line. This discovery was followed by the identification of the 2-(4-amino-3-methylphenyl)benzothiazole (DF 203, NSC 674495) and 2-(4-amino-3-methylphenyl)-5-fluorobenzothiazole (5F 203, NSC 703786) and the evaluation of the analogue compounds with more potent and diverse activities [8][9][10][11][12][13][14] . Phortress (NSC 710305, dihydrochloride salt of the lysylamide prodrug of 2-(4-amino-3-methylphenyl)-5-fluorobenzothiazole (5F 203)), the fluorinated water-soluble pro-drug, which has been synthesized to address formulation and bioavailability issues related to the desired parenteral administration [15][16][17][18][19] , was then chosen for phase 1 The mechanism of action involves formation of reactive intermediates that can bind covalently to DNA and can be metabolized only by sensitive cancer cell lines 21 .…”

Synthesis and in vitro antiproliferative activity of new benzothiazole derivatives

“…4 Substituted 2-(4-aminophenyl)benzothiazoles were developed and examined, in vitro, for their antiproliferative activity in ovarian, breast, renal and colon carcinoma human cell lines, [5][6][7][8] imidazo benzothiazoles, 9,10 as well as, polymerized benzothiazoles 11 and other substituted benzothiazoles 12 showed remarkable antitumor activity against malignant cell lines. The aryl amines, 2-(4-amino-3-methylphenyl)benzothiazole, 13 were deduced from comparison with compounds 5a-k.…”