Novel Pyrimidine-Based Schiff Base Derivatives: Synthesis, Molecular Docking, and Cytotoxic Evaluation Against Colorectal Cancer Targeting AXL Tyrosine Kinase
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2025
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| author | R. Priyadarsini, S. Archana*, G. Guhan, J. Hanitha Mathanke |
| author_facet | R. Priyadarsini, S. Archana*, G. Guhan, J. Hanitha Mathanke |
| contents | <p><span lang="EN-US">The study aimed to design, synthesize, and evaluate a series of novel pyrimidine derivatives as potential anticancer agents targeting colorectal carcinoma, integrating both in silico and in vitro approaches to assess their pharmacological potential. Five pyrimidine derivatives (AS1–AS5) were designed and synthesized through a three-step process involving chalcone formation, cyclization to 4,6-diphenylpyrimidin-2-amine, and Schiff base condensation. Structural characterization was performed using UV–Vis, FTIR, ¹H NMR, and HRMS analyses, with purity confirmed by melting point and TLC. ADME, toxicity, and molecular docking studies against AXL tyrosine kinase (PDB ID: 5U6C) were conducted using SwissADME, Osiris Toxicity Explorer, and AutoDock 4.2, respectively. The cytotoxic potential of the compounds was evaluated on the HCT-116 colorectal cancer cell line using the MTT assay, with 5-fluorouracil as the standard. All synthesized compounds obeyed Lipinski’s rule of five and were predicted to be non-toxic. Docking results revealed good binding affinities with AXL kinase, particularly for AS-5. In vitro cytotoxicity testing demonstrated that AS-5 exhibited the highest anticancer activity with an IC₅₀ value of 18.39 µg/mL, followed by AS-4 (37.08 µg/mL) and AS-2 (44.05 µg/mL), showing dose-dependent inhibition of HCT-116 cell proliferation. The combined in silico and in vitro findings confirm that pyrimidine derivatives, especially AS-5, possess strong anticancer potential and favorable pharmacokinetic profiles. These compounds can serve as lead scaffolds for further development of targeted therapies against colorectal carcinoma. <span> </span></span></p> |
| format | Recurso digital |
| id | zenodo_https___doi_org_10_5281_zenodo_17493188 |
| institution | Zenodo |
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| publishDate | 2025 |
| publisher | Zenodo |
| record_format | zenodo |
| spellingShingle | Novel Pyrimidine-Based Schiff Base Derivatives: Synthesis, Molecular Docking, and Cytotoxic Evaluation Against Colorectal Cancer Targeting AXL Tyrosine Kinase R. Priyadarsini, S. Archana*, G. Guhan, J. Hanitha Mathanke Pyrimidine derivatives,Schiff base, AXL tyrosine kinase, colorectal cancer, MTT assay; molecular docking, ADME, cytotoxicity. <p><span lang="EN-US">The study aimed to design, synthesize, and evaluate a series of novel pyrimidine derivatives as potential anticancer agents targeting colorectal carcinoma, integrating both in silico and in vitro approaches to assess their pharmacological potential. Five pyrimidine derivatives (AS1–AS5) were designed and synthesized through a three-step process involving chalcone formation, cyclization to 4,6-diphenylpyrimidin-2-amine, and Schiff base condensation. Structural characterization was performed using UV–Vis, FTIR, ¹H NMR, and HRMS analyses, with purity confirmed by melting point and TLC. ADME, toxicity, and molecular docking studies against AXL tyrosine kinase (PDB ID: 5U6C) were conducted using SwissADME, Osiris Toxicity Explorer, and AutoDock 4.2, respectively. The cytotoxic potential of the compounds was evaluated on the HCT-116 colorectal cancer cell line using the MTT assay, with 5-fluorouracil as the standard. All synthesized compounds obeyed Lipinski’s rule of five and were predicted to be non-toxic. Docking results revealed good binding affinities with AXL kinase, particularly for AS-5. In vitro cytotoxicity testing demonstrated that AS-5 exhibited the highest anticancer activity with an IC₅₀ value of 18.39 µg/mL, followed by AS-4 (37.08 µg/mL) and AS-2 (44.05 µg/mL), showing dose-dependent inhibition of HCT-116 cell proliferation. The combined in silico and in vitro findings confirm that pyrimidine derivatives, especially AS-5, possess strong anticancer potential and favorable pharmacokinetic profiles. These compounds can serve as lead scaffolds for further development of targeted therapies against colorectal carcinoma. <span> </span></span></p> |
| title | Novel Pyrimidine-Based Schiff Base Derivatives: Synthesis, Molecular Docking, and Cytotoxic Evaluation Against Colorectal Cancer Targeting AXL Tyrosine Kinase |
| topic | Pyrimidine derivatives,Schiff base, AXL tyrosine kinase, colorectal cancer, MTT assay; molecular docking, ADME, cytotoxicity. |
| url | https://doi.org/10.5281/zenodo.17493188 |