In silico identification of natural compounds from Couroupita guianensis as anticancer congeners targeting EGFR: Molecular docking and pharmacokinetic evaluations

The fast improvement of combinatorial synthesis and high-throughput screening (HTS) has sped up drug discovery. These strategies allow for the efficient synthesis and assessment of large chemical libraries against biological targets. While these technologies show immense promise, natural products continue to be a rich reservoir of bioactive chemicals that can play an important role in drug development. Herbal treatments have long been used to produce useful medications and are still important in current drug research. There is increasing evidence that plant-based chemicals can help prevent cancer. Our study aimed to identify the most promising phytoconstituents of Couroupita guianensis capable of inhibiting the epidermal growth factor receptor (EGFR). Molecular docking, protein-ligand interactions, molecular dynamics (MD) simulation, toxicity prediction, and pharmacophore modelling techniques were used in the study. Sunitinib was used as the reference molecule. Molecular docking was performed on all 23 phytoconstituents, as well as the conventional medication and the 4HJO protein co-crystal inhibitor. Ten compounds had higher binding affinities than the standards against the EGFR protein. Apigenin (−9.7 kcal/mol) had the highest binding affinity, followed by Tryptanthrin (−9.5 kcal/mol), Ellagic acid (-9.2 kcal/mol) Couroupitine A (-9.1 kcal/mol), and Kaempferol (-9 kcal/mol). Most screened phytochemicals are non-carcinogenic, non-mutagenic, and non-cytotoxic, making Apigenin, Ellagic acid, Kaempferol, Couroupitine A, quercetin, rutin and Tryptanthrin promising candidates with minimal toxicity alerts and strong drug-likeness. The BOILED-Egg model shows that the majority of the screened compounds have good ADME behavior, especially in the high-absorption region. The molecular dynamics simulation analysis indicates that Apigenin, Kaempferol, Couroupitine A, Quercetin, Luteolin, and Tryptanthrin exhibit reduced fluctuations compared to Erlotinib indicating that these phytochemicals provide more stabilization of this binding area than Erlotinib. Subsequent pharmacophore modeling validates Apigenin, Kaempferol, Couroupitine A, and Tryptanthrin as prospective phytoconstituents for anticancer drug development. Four phytocompounds with good ADME profiles and significant binding affinities were identified by the in-silico investigation of the EGFR kinase: Apigenin, Tryptanthrin, Couroupitine A, and Kaempferol. They have structural features that improve EGFR interaction. For the development of EGFR-targeted cancer treatments, these particular molecules could be helpful scaffolds. Computational analysis of phytoconstituents of Couroupita guianensis as anticancer candidate