Background: Cancer is a major health problem worldwide and the major cause of human
mortality in the world. The identification of novel structures for effective treatment of cancer is still a
major challenge to medicinal chemists. Over the time, important milestones have been achieved in the
development of various cancer static drugs for antitumor chemotherapy. Chemotherapy is still highly
inadequate, and this necessitates to find novel compounds with potent anticancer activity and minimal
or no side effects.
Methods: 5-Amino-3-methyisoxazole 1 was treated with different salicylaldehydes 2a-d refluxing in
methanol to get the desired products 2-(3-methylisoxazol)-5-ylimino)methyl)phenols 3a-d. The reduction
of these imine intermediates with NaBH4 at room temperature produced the amino phenols 4a-d,
which underwent smooth ring closure in the presence of formaldehyde, to give isoxazolyl-1,3-
benzoxazine derivatives 5a-d. Compound 5d under Suzuki coupling conditions with different aryl and
hetero aryl boronic acids furnished the products 7a-d.
Results: We synthesized the 3,4-dihydro-8-methoxy-3-(3-methylisoxazol-5-yl)-2H-benzo[e][1,3]oxazine
derivatives 5a-5d and 7a-7d from readily accessible starting materials in excellent yields. The newly
synthesized compounds 5a-5d and 7a-7d were evaluated for in vitro and potent compounds 5b and 7b
were screened for in vivo anticancer activity. Compound 5b has shown potential anticancer activity both
in vitro and in vivo. Molecular docking studies were also carried out to balance the experimental results.
Conclusion: The structure of all newly synthesized compounds 3-5a-d and 7a-d was confirmed on the
basis of IR, 1H NMR, 13C NMR and mass spectral data. Molecular docking studies of compounds 5b
and 7b revealed their efficient binding in the hydrophobic pocket in the ATP binding site of EGFR
which is consistent with the biological data. Further studies are needed to identify the specific compounds
in the series and to develop them as potential anticancer agents.