Virtual screening of anticancer activity of chalcones and pyrazolines as potential EGFR, VEGFR, and cytochrome P450 inhibitors

Abstract

Context: Metastatic breast cancer is still categorized as an incurable disease because all available therapies are palliative treatments to relieve symptoms and increase life expectancy. Our previous study showed that N-pyrazoline-derived compounds have the potential as an antiproliferative drug in cervical cancer cells line. Therefore, virtual screening is conducted in this study to predict the anticancer potential of several molecules (chalcone and pyrazoline derivatives) against breast cancer cells before in vitro testing. Aims: To screen potential anticancer compounds of chalcone and pyrazoline derivatives through in silico approach. Methods: In this study were carried out multiple virtual screening steps to predict drug-likeness, pharmacokinetic, toxicity, and interactions between drug candidates and receptors involved cell in proliferation (EGFR, PDB.id 7LGS), angiogenesis (VEGFR1, PDB.id 3HNG; VEGFR2, PDB.id 4AG8), and oxidative stress (cytochrome P450, PDB.id 3UA1). Results: Results revealed that pyrazolines A, A1, A2, B, C2, D, and M could potentially be anticancer agents since the molecules qualify Lipinski’s rule, are predicted to have good pharmacokinetics, are indicated as harmless, and exhibit the best binding affinity based on molecular docking analysis. Conclusions: The EGFR appears to be the main pathway targeted by pyrazoline derivates. Meanwhile, the ligand will go through the VEGFR1, VEGFR2, or P450 pathways when it successfully overcomes the binding obstacle. In addition, pyrazolines A, A1, A2, B, C2, D, and M need to be synthesized and evaluated the in vitro and in vivo anticancer activity.