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Evaluation of the biological activity of novel monocationic fluoroaryl-2,2'-bichalcophenes and their analogues.

Hussin WA, Ismail MA, Alzahrani AM, El-Sayed WM - Drug Des Devel Ther (2014)

Bottom Line: The fluoroaryl derivatives significantly reduced the NaN3-induced and B[a]P-induced mutagenicity under pre-exposure and co-exposure conditions.Monocationic fluoroarylbichalcophenes were superior to the corresponding mononitriles in reducing B[a]P-induced mutagenicity.Some of these compounds could be selected for further anticancer studies.

View Article: PubMed Central - PubMed

Affiliation: King Faisal University, College of Science, Departments of Chemistry and Biological Sciences, Hofuf, Saudi Arabia ; Al-Azhr University, Faculty of Science, Department of Botany and Microbiology, Cairo, Egypt.

ABSTRACT
A series of bichalcophene fluorobenzamidines 5a-e was synthesized from the corresponding mononitriles 4a-e via a direct reaction with lithium bis(trimethylsilyl)amide LiN(TMS)2 followed by de-protection with ethanolic HCl (gas). Bichalcophene fluorobenzonitriles 4a-e were prepared adopting a Stille coupling reaction between the bromo compounds 3a-c and 2-(tri-n-butylstannyl)furan or analogues. As an approach to drug discovery, the structure-antimutagenicity relationship of novel fluoroarylbichalcophenes was examined using the Ames Salmonella/microsomal assay. At nontoxic concentrations (10 and 20 μM), all derivatives alone or in combination with sodium azide (NaN3; 2 μg/plate) or benzo[a]pyrene (B[a]P; 20 μM) in the presence of S9 mix were not mutagenic. The fluoroaryl derivatives significantly reduced the NaN3-induced and B[a]P-induced mutagenicity under pre-exposure and co-exposure conditions. The recorded antimutagenic activity of fluoroaryl derivatives varied depending on the kind of mutagen and the exposure regimen. Monocationic fluoroarylbichalcophenes were superior to the corresponding mononitriles in reducing B[a]P-induced mutagenicity. Nevertheless, mononitriles were more active against NaN3, especially at low concentrations and under pre-exposure treatments. The antimutagenic activity was congruent with a high antioxidant activity that could promote the DNA repair system. The fluorine substitution changed the antimutagenic signature of bichalcophenes. Some of these compounds could be selected for further anticancer studies.

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Synthesis of novel monocationic fluoroaryl-2,2′-bichalcophene derivatives.
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f2-dddt-8-963: Synthesis of novel monocationic fluoroaryl-2,2′-bichalcophene derivatives.

Mentions: A series of bichalcophene fluorobenzamidines 5a–e was prepared from the corresponding mononitriles 4a–e by direct reaction with LiN(TMS)2 (Figure 2). Thus, compound 4-(2,2′-bifuran-5-yl)-3-fluorobenzamidine (5a) was obtained from the corresponding mononitrile 4a by treatment with LiN(TMS)2 followed by deprotection with ethanolic HCl (gas). The structures of fluorobenzamidines 5a–e were identified by their spectroscopic and elemental analyses. Thus, 1H NMR spectrum of compound 5a displayed singlet signal at δ 9.44 (4H) characteristic for the cationic amidine group in addition to the signals corresponding to the trisubstituted benzene ring and bifuran moiety. Fluoroarylbichalcophene mononitriles 4a–e were prepared adopting a Stille coupling reaction between the corresponding bromo compounds 3a–c and 2-(tri-n-butylstannyl)furan or analogues using our previously described methodology for the preparation of non-fluorinated bichalcophene analogues.18 The structures of compounds 4a–e were assigned based on their spectral and elemental analyses.


Evaluation of the biological activity of novel monocationic fluoroaryl-2,2'-bichalcophenes and their analogues.

Hussin WA, Ismail MA, Alzahrani AM, El-Sayed WM - Drug Des Devel Ther (2014)

Synthesis of novel monocationic fluoroaryl-2,2′-bichalcophene derivatives.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4109633&req=5

f2-dddt-8-963: Synthesis of novel monocationic fluoroaryl-2,2′-bichalcophene derivatives.
Mentions: A series of bichalcophene fluorobenzamidines 5a–e was prepared from the corresponding mononitriles 4a–e by direct reaction with LiN(TMS)2 (Figure 2). Thus, compound 4-(2,2′-bifuran-5-yl)-3-fluorobenzamidine (5a) was obtained from the corresponding mononitrile 4a by treatment with LiN(TMS)2 followed by deprotection with ethanolic HCl (gas). The structures of fluorobenzamidines 5a–e were identified by their spectroscopic and elemental analyses. Thus, 1H NMR spectrum of compound 5a displayed singlet signal at δ 9.44 (4H) characteristic for the cationic amidine group in addition to the signals corresponding to the trisubstituted benzene ring and bifuran moiety. Fluoroarylbichalcophene mononitriles 4a–e were prepared adopting a Stille coupling reaction between the corresponding bromo compounds 3a–c and 2-(tri-n-butylstannyl)furan or analogues using our previously described methodology for the preparation of non-fluorinated bichalcophene analogues.18 The structures of compounds 4a–e were assigned based on their spectral and elemental analyses.

Bottom Line: The fluoroaryl derivatives significantly reduced the NaN3-induced and B[a]P-induced mutagenicity under pre-exposure and co-exposure conditions.Monocationic fluoroarylbichalcophenes were superior to the corresponding mononitriles in reducing B[a]P-induced mutagenicity.Some of these compounds could be selected for further anticancer studies.

View Article: PubMed Central - PubMed

Affiliation: King Faisal University, College of Science, Departments of Chemistry and Biological Sciences, Hofuf, Saudi Arabia ; Al-Azhr University, Faculty of Science, Department of Botany and Microbiology, Cairo, Egypt.

ABSTRACT
A series of bichalcophene fluorobenzamidines 5a-e was synthesized from the corresponding mononitriles 4a-e via a direct reaction with lithium bis(trimethylsilyl)amide LiN(TMS)2 followed by de-protection with ethanolic HCl (gas). Bichalcophene fluorobenzonitriles 4a-e were prepared adopting a Stille coupling reaction between the bromo compounds 3a-c and 2-(tri-n-butylstannyl)furan or analogues. As an approach to drug discovery, the structure-antimutagenicity relationship of novel fluoroarylbichalcophenes was examined using the Ames Salmonella/microsomal assay. At nontoxic concentrations (10 and 20 μM), all derivatives alone or in combination with sodium azide (NaN3; 2 μg/plate) or benzo[a]pyrene (B[a]P; 20 μM) in the presence of S9 mix were not mutagenic. The fluoroaryl derivatives significantly reduced the NaN3-induced and B[a]P-induced mutagenicity under pre-exposure and co-exposure conditions. The recorded antimutagenic activity of fluoroaryl derivatives varied depending on the kind of mutagen and the exposure regimen. Monocationic fluoroarylbichalcophenes were superior to the corresponding mononitriles in reducing B[a]P-induced mutagenicity. Nevertheless, mononitriles were more active against NaN3, especially at low concentrations and under pre-exposure treatments. The antimutagenic activity was congruent with a high antioxidant activity that could promote the DNA repair system. The fluorine substitution changed the antimutagenic signature of bichalcophenes. Some of these compounds could be selected for further anticancer studies.

Show MeSH
Related in: MedlinePlus