Research: HAMDY and COLLEAGUES,

Listed in Issue 247

Abstract

HAMDY and COLLEAGUES, (1)Applied Organic Chemistry Department, National Research Centre, Dokki,12622  Cairo, Egypt; (2)Therapeutical Chemistry Department, National Research Centre, Dokki, 12622 Cairo, Egypt; (3)Photochemistry Department, National Research Centre, Dokki, 12622 Cairo, Egypt; (4)Department of Tanning Materials and Leather Technology, National Research Centre, Dokki, 12622 Cairo, Egypt evaluated the antioxidant activity of newly synthesized compounds and screened for tumour inhibitory activity against liver cancer cells compared the reference drug doxorubicin.

Background

2-Acetyl-5,6,7,8-tetrahydronaphthalene (1) was allowed to react with different aromatic aldehydes to produce the cyanopyridones 2a and 2b, which were treated with phosphorous pentasulfide to afford the corresponding thioxopyridine derivatives 3a and 3b, respectively. The reaction of 3a and 3b with ethyl bromoacetate afforded the ester derivatives 4a and 4b, while their condensation with hydrazine hydrate gave the corresponding pyrazolopyridine derivatives 5a and 5b.

Methodology

The reaction of the precursor 2-amino-5,6,7,8-tetrahydronaphthalene (6) with ethoxy methylenemalonic ester led to the formation of aminomethylenemalonate derivative 7. Cyclization of 7 in boiling diphenyl ether gave the derivative - ethyl 6,7,8,9-tetrahydro-4-hydroxybenzo[g]-quinoline-3-carboxylate (8) which was hydrolyzed to produce the corresponding carboxylic acid analogue 9. Further reaction of 3a with 3-chloropropane-1,2-diol and/or iodomethane produced the corresponding nicotinonitrile derivatives 10 and 11. Hydrazinolysis of derivative 11 gave the hydrazinyl derivative 12.

Results

Moreover, chlorination of compound 2a with phosphorous oxychloride led to 2-chloro nicotinonitrile derivative 13, which was refluxed with various amines to form the corresponding derivatives 5a, 14 and 15. Treatment of the pyrazolopyridine compound 5a with formic acid and acetic anhydride afforded the corresponding formamide and acetamide analogues 16 and 17, while its reaction with DMF-DMA yielded the corresponding formimidamide derivative 18. The pyridopyrazolo[1,5-a]pyrimidine derivative 19 was obtained by cyclization of 5a with acetyl acetone.

Conclusion

The antioxidant activity evaluation of the newly synthesized compounds showed that the pyrazolopyridine derivative 5a exhibited scavenging potency higher than that obtained by ascorbic acid. Tumour inhibitory activity screening revealed that derivatives 8 and 10 showed promising potency against the liver cancer cells (HepG-2) compared to doxorubicin as a reference drug.

References

Hamdy NA(1), Anwar MM(2), Abu-Zied KM(3), Awad HM(4). Synthesis, tumor inhibitory and antioxidant activity of new polyfunctionally  2-substituted 5,6,7,8-tetrahydronaphthalene derivatives containing pyridine,  thioxopyridine and pyrazolopyridine moieties. Acta Pol Pharm. 70(6):987-1001. Nov-Dec 2013.

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