Synthesis, Molecular Docking studies, Anticancer and Anti-Inflammatory Activity of Tetrazole Linked Isoxazolo[5,4-B]Pyridines
K Thirupathaiah
Department of Chemistry, M. V. S. Government Arts and Science College (A), Mahabubnagar – 509001, Telangana, India.
G Satyanarayana Goud
Department of Chemistry, M. V. S. Government Arts and Science College (A), Mahabubnagar – 509001, Telangana, India.
N Venu Gopal
Department of Chemistry, M. V. S. Government Arts and Science College (A), Mahabubnagar – 509001, Telangana, India.
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http://doi.org/10.37648/ijps.v16i01.009
Abstract
Objective: A series of tetrazole linked isoxazolo[5,4-b]pyridines were synthesized, and their anticancer, anti-inflammatory activity, and molecular docking studies were evaluated. Methods: The one-pot reaction of 5-amino-3-methylisoxazole 1, substituted aromatic aldehyde 2, and benzoyl acetonitrile 3 in presence of Fecl3 on basic alumina (1:2 equiv.) furnished 3-methyl-4-aryl-6-phenylisoxazolo[5,4-b]pyridine-5-carbonitriles 4. Compounds 4 on reaction with benzyl azides in presence of saturated copper sulfate solution and Cu-turnings in ethanol afforded the title compounds viz., 5-(2-benzyl-2H-tetrazol-5-yl)-3-methyl-4-aryl-6-phenylisoxazolo[5,4-b]pyridines 5a-l. The anticancer activity of the synthesized compounds was determined using MTT assay for in vitro studies, liquid tumor model for in vivo activity. The anti-inflammatory activity and molecular docking studies has been carried out. Results and Discussion: The structures of newly synthesized derivatives were confirmed by IR, 1H, 13C NMR and mass spectrometry. In anticancer activity as well as in anti-inflammatory studies, among all the derivatives 5a-l, 5c, 5d exhibited potent activity against the HeLa, EAC and MCF-7 cell lines. They also demonstrated significant in vitro cyclooxygenase inhibition (COX-1, COX-2) during anti-inflammatory activity. These results very well supported by molecular docking analysis. Conclusions: A new series of tetrazole linked isoxazolo[5,4-b]pyridines were developed and investigated for in vitro and in vivo anticancer activity, anti-inflammatory activity, and molecular docking studies. Compounds 5c, 5d showed promising results in both anticancer and anti-inflammatory assays, and the results are very well supported by molecular docking analysis. These scaffolds, with further structural modification, hold potential candidates for cancer and inflammatory therapeutics.
Keywords:
Three-component synthesis; tetrazole linked isoxazolo[5,4-b]pyridines; anticancer agents; anti-inflammatory activity; molecular docking studies; cyclooxygenase inhibition studies.
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