2-(4-Amino-3-methylphenyl)-5-fluorobenzothiazole is a ligand and shows species-specific partial agonism of the aryl hydrocarbon receptor

Bazzi, Rana; Bradshaw, Tracey D.; Rowlands, J. Craig; Stevens, Malcolm F. G.; Bell, David R.

doi:10.1016/j.taap.2009.02.015

Cited by 31 publications

(23 citation statements)

References 34 publications

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“…In the related context of pharmacological interactions, Bazzi et al, identified a possible mechanism of action for the antiproliferative effect of phenylbenzothiazoles, which can be attributed to CYP1 family-mediated metabolism [66]. They suggested that the AhR signaling pathway may be involved in mediating the anticancer activity of novel 2-(4-aminophenyl) benzothiazole drugs in MCF-7 breast cancer cells.…”

Section: A Pharmacological Interactions Between Phenylbenzothiazolementioning

confidence: 99%

Benzothiazoles: How Relevant in Cancer Drug Design Strategy?

Singh¹,

Singh²

2014

ACAMC

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Heterocyclic compounds, analogs and derivatives have attracted attention due to their diverse biological and pharmacological properties. Benzoheterocycles such as benzothiazoles, benzimidazoles and benzoxazoles are constituents of many bioactive heterocyclic compounds, having wider range of applications. They have been extensively studied for their biological activities, and can serve as unique and versatile scaffolds for drug design. The benzothiazole, in the family of heterocyclic compounds has assumed special significance in synthetic chemistry, pharmaceutical chemistry as well as in clinical applications because of its anti-tumor properties. This review is organized in the following ways. It begins with brief introduction on the chemical diversity of synthetic analogs of benzothiazole. After this, drug design strategy and mechanisms of action through its diverse biological targets in which benzothiazole and its derivatives display their anticancer activity are discussed. It ends with the metabolism pattern of benzothiazole and its analogs. Analysis of the structure-activity relationships (SAR), quantitative structure-activity relationships (QSAR) as well as on docking studies of this family of compounds highlights the potential that may lead to the development of novel anticancer agents. Such relationships will definitely create lot of interest among the researchers to synthesize optimized variety of benzothiazole derivatives and to screen them for their anticancer activity.

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Section: A Pharmacological Interactions Between Phenylbenzothiazolementioning

confidence: 99%

Benzothiazoles: How Relevant in Cancer Drug Design Strategy?

Singh¹,

Singh²

2014

ACAMC

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“…Thus, the spectrum of activity of this bis-methyl ether extends to human cell lines derived from intractable colorectal carcinomas (CRC). A potent AhR ligand (K i ¼ 6.8 nmol/L), GW-610 is sequestered exclusively and rapidly by sensitive breast and CRC cells only (9,10).…”

Section: Introductionmentioning

confidence: 99%

CYP2S1 and CYP2W1 Mediate 2-(3,4-Dimethoxyphenyl)-5-Fluorobenzothiazole (GW-610, NSC 721648) Sensitivity in Breast and Colorectal Cancer Cells

Tan

Tiong

Muruhadas

et al. 2011

Molecular Cancer Therapeutics

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Both 2-(4-amino-3-methylphenyl)-5-fluorobenzothiazole (5F-203; NSC 703786) and 2-(3,4-dimethoxyphenyl)-5-fluorobenzothiazole (GW-610; NSC 721648) are antitumor agents with novel mechanism(s). Previous studies have indicated that cytochrome (CYP) P450 1A1 is crucial for 5F-203 activity. In the present study, we investigated the functional role of 2 newly identified CYP P450 enzymes, CYP2S1 and CYP2W1, in mediating antitumor activity of benzothiazole compounds. We generated isogenic breast cancer (MDA-MB-468, MCF-7) and colorectal cancer (CRC; KM12 and HCC2998) cell lines depleted for CYP1A1, CYP2S1, or CYP2W1. The sensitivity of these cells to 5F-203 and GW-610 was then compared with vector control cells. 5F-203 exhibited potent activity against breast cancer cells, whereas GW-610 was effective against both breast and colorectal cancer cells. CYP1A1 was induced in both breast cancer and CRC cells, while CYP2S1 and CYP2W1 were selectively induced in breast cancer cells only following treatment with 5F-203 or GW-610. Depletion of CYP1A1 abrogated the sensitivity of breast cancer and CRC cells to 5F-203 and GW-610. Although depletion of CYP2S1 sensitized both breast cancer and CRC cells toward 5F-203 and GW-610, CYP2W1 knockdown caused marked resistance to GW-610 in CRC cells. Our results indicate that CYP-P450 isoforms, with the exception of CYP1A1, play an important role in mediating benzothiazole activity. CYP2S1 appears to be involved in deactivation of benzothiazoles, whereas CYP2W1 is important for bioactivation of GW-610 in CRC cells. Because CYP2W1 is highly expressed in colorectal tumors, GW-610 represents a promising agent for CRC therapy. Mol Cancer Ther; 10(10); 1982-92. Ó2011 AACR.

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“…The statistical results are derived from one-way ANOVA/Tukey's multiple range tests. treatment periods increase the risk of chemical metabolism, and may affect potency estimates (Bazzi et al, 2009;DeGroot et al, 2015). In this case, we propose that BDE-99 is a transient Ahr agonist.…”

Section: Discussionmentioning

confidence: 95%

BDE-99, but not BDE-47, is a transient aryl hydrocarbon receptor agonist in zebrafish liver cells

Yang

Zhu

Chan

2016

Toxicology and Applied Pharmacology

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2-(4-Amino-3-methylphenyl)-5-fluorobenzothiazole is a ligand and shows species-specific partial agonism of the aryl hydrocarbon receptor

Abstract: Non-standard abbreviations.2-(4-amino-3-methylphenyl)-5-fluorobenzothiazole, 5F 203; tetrachloroazoxybenzene, TCAOB; 2,3,7,

Cited by 31 publications

References 34 publications

Benzothiazoles: How Relevant in Cancer Drug Design Strategy?

Benzothiazoles: How Relevant in Cancer Drug Design Strategy?

CYP2S1 and CYP2W1 Mediate 2-(3,4-Dimethoxyphenyl)-5-Fluorobenzothiazole (GW-610, NSC 721648) Sensitivity in Breast and Colorectal Cancer Cells

BDE-99, but not BDE-47, is a transient aryl hydrocarbon receptor agonist in zebrafish liver cells

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