Novel coumarin amino acid derivatives: Design, synthesis, docking, absorption, distribution, metabolism, elimination, toxicity (ADMET), quantitative structure–activity relationship (QSAR) and anticancer studies

Abstract

Purpose: Obtain a new safe anticancer agent based on the coumarin derivatives. Methods: DFT, docking, MD simulations were used for designing the new compounds. Docking was performed to identify the molecular interaction between the compounds-receptor. The anticancer study in vitro was evaluated against (MCF-7). The QSAR model was predicted based on; chemical reactivity. Results: The compounds 3, 5–7, 10–12 and 14–16 represented a significant interaction score through Docking experiment. The stability of docked ligands was examined through molecular dynamic simulation, which showed high stability for tested compounds into active site. These compounds were elected for further Drug studies as likeness and ADME/T, which proposed that these ligands may have a good pharmacokinetic character with no carcinogenic effect. The compounds 15 and 16 (IC50 = 0.49 and 0.52 M) exhibited the highest anticancer potency among all tested compounds. The compounds 3, 5, 7 and 10 showed higher activity than reference drug. The promising activity for synthesized compounds may be explained by increasing hydrophobicity for these compounds. The QSAR "Quantitative Structure Activity Relationship" model has been predicted to investigate the structural requirements of MCF-7-inhibitions. This model is statistically significant with good predictive power. Statistical QSAR derivative model with good predictive power. Conclusion: This study introduces experimental indication toward investigation of the synthesized compounds as the candidate of cancer therapy.