Structural studies on benzothiazoles. Crystal and molecular structure of 5,6-dimethoxy-2-(4-methoxyphenyl-benzothiazole and molecular orbital calculations on related compounds.

Yates, Paul C.; McCall, Carol J.; Stevens, Malcolm F. G.

doi:10.1016/s0040-4020(01)86576-5

Cited by 27 publications

(17 citation statements)

References 5 publications

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“…We have previously reported on the biological properties of polyhydroxylated 2-phenylbenzothiazoles (Stevens et al, 1994), which were originally designed as potential tyrosine kinase inhibitors modelled on structural comparisons with the flavone quercetin and isoflavone genistein (Yates et al, 1991). 2-(4-Aminophenyl)benzothiazole (CJM 126) (Figure 1), prepared as a synthetic intermediate in this programme, was found to elicit pronounced inhibitory effects against certain breast cancer cell lines in vitro with an intriguing biphasic dose-response relationship .…”

mentioning

confidence: 99%

2-(4-Aminophenyl)benzothiazoles: novel agents with selective profiles of in vitro anti-tumour activity

Bradshaw

Wrigley²,

Shi³

et al. 1998

Br J Cancer

217

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Summary 2-(4-Aminophenyl)benzothiazole (CJM 126) elicits biphasic growth-inhibitory effects against a panel of oestrogen receptor-positive (ER+) and oestrogen receptor-negative (ER-) human mammary carcinoma cell lines in vitro, yielding IC50 values in the nm range. Substitutions adjacent to the amino group in the 2-phenyl ring with a halogen atom or methyl group enhance potency in sensitive breast lines (pM IC50 values). Transient biphasic dose responses were induced but rapidly eradicated after specific drug exposure periods. Two human prostate carcinoma cell lines were refractory to the growth-inhibitory properties of 2-(4-aminophenyl)benzothiazoles; IC50 values > 30 ,UM were obtained.Potency and selectivity were confirmed when compounds were examined in the National Cancer Institute's Developmental Therapeutics screen; the spectrum of activity included specific ovarian, renal, colon as well as breast carcinoma cell lines. Moreover, comparing 6-day and 48-h incubations, the exposure time-dependent nature of the biphasic response was corroborated. Differential perturbation of cell cycle distribution followed treatment of MCF-7 and MDA 468 cells with substituted 2-(4-aminophenyl)benzothiazoles. In MDA 468 populations only, accumulation of events in G/M phase was observed. Two MCF-7 cell lines were established with acquired resistance to CJM 126 (IC50 values > 20 gM), which exhibit cross-resistance to substituted benzothiazoles, but equal sensitivity to tamoxifen and doxorubicin. Compared with standard anti-tumour agents evaluated in the National Cancer Institute in vitro cell panel, benzothiazoles revealed unique profiles of growth inhibition, suggesting a mode(s) of action shared with no known clinically active class of chemotherapeutic agents.

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mentioning

confidence: 99%

2-(4-Aminophenyl)benzothiazoles: novel agents with selective profiles of in vitro anti-tumour activity

Bradshaw

Wrigley²,

Shi³

et al. 1998

Br J Cancer

217

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“…2-(4-Aminophenyl)benzothiazole (CJM 126, Figure 1) was originally prepared as a synthetic intermediate within a programme to design potential tyrosine kinase inhibitors modelled on structural comparisons with the flavone quercetin and isoflavone genistein (Yates et al, 1991;Stevens et al, 1994). It was found to elicit potent inhibitory effects against breast cancer cell lines in vitro, yielding biphasic dose-response profiles (Shi et al, 1996).…”

mentioning

confidence: 99%

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

Bradshaw

Shi²,

Schultz³

et al. 1998

Br J Cancer

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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

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“…In another patent, Jackson et al have reported 2-arylamino benzothiazole derivatives (20) as activators of pro-matrix metalloproteinase [43]. Imide-linked benzothiazoles have also been studied and patented for anticancer activities.…”

Section: Benzothiazole Derivatives As Anticancer Agentsmentioning

confidence: 99%

“…In one of the first reports, Stevens et al have synthesized polyhydroxylated 2-phenylbenzothiazoles [20,21] to serve as surrogates for the naturally occurring bioactive flavonoid, quercetin and isoflavone genistein. These polyhydroxylated 2-phenylbenzothiazoles lacked mimicking of the ATP antagonistic effects and tyrosine kinase inhibition.…”

Section: Introductionmentioning

confidence: 99%

Therapeutic potential of benzothiazoles: a patent review (2010 – 2014)

Kamal

Syed

Mohammed

2015

Expert Opinion on Therapeutic Patents

120

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Several molecules containing benzothiazole skeleton are agents of choice for the treatment of various human diseases/disorders. Its versatile character of being capable of serving as ligand to various biomolecules attracted the interest of medicinal chemists for the development of therapies for respective ailments, especially, the 2-arylbenzothiazole moiety which is under development for the treatment of cancer. This signifies the increasing importance of benzothiazole nucleus in the area of drug discovery. Its structural simplicity and ease of synthesis provides scope for the development of chemical libraries that could serve in the discovery of new chemical entities progressing towards the market.

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Structural studies on benzothiazoles. Crystal and molecular structure of 5,6-dimethoxy-2-(4-methoxyphenyl-benzothiazole and molecular orbital calculations on related compounds.

Cited by 27 publications

References 5 publications

2-(4-Aminophenyl)benzothiazoles: novel agents with selective profiles of in vitro anti-tumour activity

2-(4-Aminophenyl)benzothiazoles: novel agents with selective profiles of in vitro anti-tumour activity

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

Therapeutic potential of benzothiazoles: a patent review (2010 – 2014)

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