Design and Synthesis of Substituted Anilino 6-(3,4,5-Trimethoxyphenyl)Pteridine Derivatives and Invitro Evaluation as Potential Cytotoxic Agents.

Abstract A new library of target compounds (<bold>9a-j</bold>) was designed, synthesized, and fully characterized by 1HNMR, 13CNMR, and mass spectroscopy techniques. The target compounds were screened for their cytotoxic properties against cancer cell lines Colo-205, MCF-7, A549, and A2780 by employing the MTT assay, using the etoposide as the positive control. Among the newly synthesized target compounds, four compounds <bold>9b-9d</bold> and <bold>9j</bold> exhibited superior cytotoxic properties to the reference standard (etoposide). In particular, compound <bold>9b</bold> was more cytotoxic against all four cell lines with IC50 in the range of 0.016 to 0.17 μM. Further 9b is more selective toward A549 and followed by MCF-7. Molecular docking studies of all the target compounds were carried out against hDHFR to see the binding interactions and binding affinities. Ligands <bold>9b</bold> and <bold>9c</bold> have the highest binding affinities toward hDHFR and these results substantiate the experimental findings. The MEC was analyzed for the most potent compounds <bold>9b</bold> and <bold>9c</bold>. All the ligands have passed the Insilico ADME properties and haven‘t violated more than one Ro5. [ABSTRACT FROM AUTHOR]