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 (9a-j) 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 9b-9d and 9j exhibited superior cytotoxic properties to the reference standard (etoposide). In particular, compound 9b 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 9b and 9c have the highest binding affinities toward hDHFR and these results substantiate the experimental findings. The MEC was analyzed for the most potent compounds 9b and 9c. All the ligands have passed the Insilico ADME properties and haven‘t violated more than one Ro5.

Keywords:

• Pteridine
• methotrexate
• etoposide
• hDHFR
• ADME
• molecular electrostatic complementarity

Acknowledgment

The authors thank the Department of Pharmaceutical Chemistry, Telangana University for providing the research lab facilities.

Author contributions

GSK: Synthesis, Data Acquisition; GS: MTT Assay, Writing; GK: Docking Studies, Insilico Studies, Writing; KS: Docking Studies, Insilico Studies, Analysis; GR: MEC, Analysis; NR: Synthesis, Analysis; BS: Study Design, Docking, Writing; VCS: Study Design, Analysis; MS: Design, Writing, Reviewing, Editing.

Disclosure statement

No potential conflict of interest was reported by the author(s).