Abstract
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.
Keywords: Isoxazolyl-1, 3-benzoxazine, Suzuki-Miyura coupling, anticancer activity, Ehrlich Ascites Carcinoma (EAC), Epidermal Growth Factor Receptor (EGFR).
Graphical Abstract
Letters in Organic Chemistry
Title:Synthesis and Biological Evaluation of 3,4-Dihydro-3-(3-methylisoxazol-5- yl)-2H-benzo[e][1,3]oxazine Derivatives as Anticancer Agents
Volume: 15 Issue: 2
Author(s): Ramu Kakkerla*, Srinivas Marri, M.P.S. Murali Krishna, Parusharamulu Molgara and Y.N. Reddy
Affiliation:
- Department of Chemistry, Satavahana University, Karimnagar-505001, Telangana,India
Keywords: Isoxazolyl-1, 3-benzoxazine, Suzuki-Miyura coupling, anticancer activity, Ehrlich Ascites Carcinoma (EAC), Epidermal Growth Factor Receptor (EGFR).
Abstract: 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.
Export Options
About this article
Cite this article as:
Kakkerla Ramu *, Marri Srinivas , Krishna Murali M.P.S. , Molgara Parusharamulu and Reddy Y.N. , Synthesis and Biological Evaluation of 3,4-Dihydro-3-(3-methylisoxazol-5- yl)-2H-benzo[e][1,3]oxazine Derivatives as Anticancer Agents, Letters in Organic Chemistry 2018; 15 (2) . https://dx.doi.org/10.2174/1570178614666170623121207
DOI https://dx.doi.org/10.2174/1570178614666170623121207 |
Print ISSN 1570-1786 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-6255 |

- Author Guidelines
- Bentham Author Support Services (BASS)
- Graphical Abstracts
- Fabricating and Stating False Information
- Research Misconduct
- Post Publication Discussions and Corrections
- Publishing Ethics and Rectitude
- Increase Visibility of Your Article
- Archiving Policies
- Peer Review Workflow
- Order Your Article Before Print
- Promote Your Article
- Manuscript Transfer Facility
- Editorial Policies
- Allegations from Whistleblowers
Related Articles
-
Recent Clinical Experience with Oncolytic Viruses
Current Pharmaceutical Biotechnology Paclitaxel (Taxol) and Taxoid Derivates for Lung Cancer Treatment: Potential for Aerosol Delivery
Current Cancer Drug Targets Increased [11C]Choline Uptake in Bronchioloalveolar Cell Carcinoma with Negative [18F]FDG Uptake. A PET/CT and Pathology Study
Current Radiopharmaceuticals Comparison of the Growth Curves of Cancer Cells and Cancer Stem Cells
Current Stem Cell Research & Therapy Stilbenes and Xanthones from Medicinal Plants as Potential Antitumor Agents
Current Bioactive Compounds Ferroptosis: A Novel Mechanism of Artemisinin and its Derivatives in Cancer Therapy
Current Medicinal Chemistry Recent Development in Indole Derivatives as Anticancer Agent: A Mechanistic Approach
Anti-Cancer Agents in Medicinal Chemistry Design, Synthesis and Molecular Modeling Studies of Some Heterocyclic Compounds Derived from the Suzuki-coupling of 6-bromo-1,3,4-oxadiazine Together with their Antitumor and Anti-leishmanial Evaluations
Current Organic Chemistry Growth Factor/Peptide Receptor Imaging for the Development of Targeted Therapy in Oncology
Current Pharmaceutical Design Molecular Targets of FoxP3+ Regulatory T Cells
Mini-Reviews in Medicinal Chemistry An Overview of Nanoformulated Nutraceuticals and their Therapeutic Approaches
Current Nutrition & Food Science Self-Assembled Micelles of Amphiphilic PEGylated Drugs for Cancer Treatment
Current Drug Targets FLT3 Inhibitors in the Management of Acute Myeloid Leukemia
Anti-Cancer Agents in Medicinal Chemistry Malignancy Risk in Systemic Lupus: Recent Research and Ongoing Challenges
Current Rheumatology Reviews Epidermal Growth Factor Receptor and its Trafficking Regulation by Acetylation: Implication in Resistance and Exploring the Newer Therapeutic Avenues in Cancer
Current Topics in Medicinal Chemistry Targeting Focal Adhesion Kinase in Neuroblastoma
Anti-Cancer Agents in Medicinal Chemistry The Role of microRNAs in the Diagnosis and Treatment of Malignant Pleural Mesothelioma - A Short Review
MicroRNA Meet Our Section Editor
Technology Transfer and Entrepreneurship (Discontinued) Novel Hybrid Molecules of Isoxazole Chalcone Derivatives: Synthesis and Study of in vitro Cytotoxic Activities
Letters in Drug Design & Discovery Obesity and Cancer: Biological Links and Treatment Implications
Current Cancer Drug Targets