Hydrolysis and photolysis of 4-Acetoxy-4-(benzothiazol-2-yl)-2,5-cyclohexadien-1-one, a model anti-tumor quinol ester.

doi:10.1021/jo9008436

Paper

Hydrolysis and photolysis of 4-Acetoxy-4-(benzothiazol-2-yl)-2,5-cyclohexadien-1-one, a model anti-tumor quinol ester.

Published May 28, 2009 · Yue-ting Wang, K. Jin, Lauren R Myers

The Journal of organic chemistry

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Abstract

4-Acetoxy-4-(benzothiazol-2-yl)-2,5-cyclohexadien-1-one, 1, a quinol derivative that exhibits significant anti-tumor activity against human breast, colon, and renal cancer cell lines, undergoes hydrolysis in aqueous solution to generate an oxenium ion intermediate, 3, that is selectively trapped by N(3)(-) in an aqueous environment. The 4-(benzothiazol-2-yl) substituent slows the rate of ionization of 1 compared to analogues with 4-phenyl or 4-(p-tolyl) substituents, 4a or 4b. However, once generated, 3 is somewhat more selective than the 4-phenyl-substituted cation 5a. Calculations performed at the B3LYP/6-31G(d) level agree that the 4-(benzothiazol-2-yl) substituent does significantly stabilize 3. The structure of the major isolated azide adduct, 4-(6-azidobenzothiazol-2-yl)phenol, 9, confirms that the positive charge is highly delocalized in 3. The results of hydrolysis of 1 show that the 4-(benzothiazol-2-yl) substituent has a significant inductive electron-withdrawing effect as well as a significant resonance effect that is electron-donating. Photolysis of 1 in aqueous solution generates the quinol 2 as one of several photolysis products. The presence of the quinol suggests that photolysis also leads, in part, to generation of 3, but photoionization of 1 is significantly less efficient than is the case for the esters 4a and 4b. This study proves that 3 is generated by ionization of 1 in an aqueous environment. A significant number of other 2-benzothiazole derivatives that are not quinols, including ring-substituted derivatives of 2-(4-aminophenyl)benzothiazole 15, are under development as anti-tumor agents as well. The possible generation of the reactive intermediate 17 by hydrolysis of the putative metabolite 16 is under investigation.

In Vitro Study

Study Snapshot

4-Acetoxy-4-(benzothiazol-2-yl)-2,5-cyclohexadien-1-one shows significant anti-tumor activity against human breast, colon, and renal cancer cell lines, with a more selective oxenium ion intermediate generated by hydrolysis and

PopulationOlder adults (50-71 years)

Sample size24

MethodsObservational

OutcomesBody Mass Index projections

ResultsSocial networks mitigate obesity in older groups.

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Paper

Hydrolysis and photolysis of 4-Acetoxy-4-(benzothiazol-2-yl)-2,5-cyclohexadien-1-one, a model anti-tumor quinol ester.

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References

Citations

Iron(III)-Catalyzed Regioselective Synthesis of Electron-Rich Benzothiazoles from Aryl Isothiocyanates via C-H Functionalization.

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Red and blue emitting fluorescent probe for cyanide and hypochlorite ions: Biological sensing and environmental analysis

The novel chemosensor P effectively detects hypochlorite and cyanide ions in biological and environmental samples, offering a promising solution for rapid and accurate detection in these environments.

Reactions of p‐Quinols with Aldehydes and Imines: Stereoselective Access to Polyheterobicyclic and Tricyclic Systems

P-quinols can selectively synthesize polyheterobicyclic and tricyclic systems in a one-pot procedure using catalysts and solvents like MeOH, tetrahydrofuran, or dichloromethane.

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2-arylbenzothiazole derivatives effectively detect specific enzyme activities in bacteria, allowing for the identification of clinically important Gram-negative and Gram-positive species.

Reversible formation of aryloxenium ions from the corresponding quinols under acidic conditions

Under acidic conditions, quinols can generate oxenium ions, which can be detected using Br-trapping methods, but not from quinols with benzothiazol-2-yl groups.

Reactions of a putative metabolite of the model antitumor drug 2‐(4‐aminophenyl)benzothiazole with purines and pyrimidines

The selective antitumor activity of 2-(4-aminophenyl)benzothiazole and its derivatives is not due to an unusual property of the nitrenium ion.