Molecular docking and dynamic simulation to identify potential phytocompound inhibitors for EGFR and HER2 as anti-breast cancer agents.

Breast cancer is the most prevalent cancer in women worldwide. To treat human breast cancer by inhibiting EGFR and HER2 targets is an important therapeutic option. Phytochemicals are found to have beneficial health effects in treating various diseases. An effort has been made to virtually screen phytochemical inhibitor by molecular docking and dynamic simulation in the current studies. The docking scores analysis resulted in a common hit Panaxadiol ligand with a low dock score for EGFR and HER2 targets. The inhibitory action of the phytocompounds was also validated by comparing it with the reference compounds Erlotinib for EGFR and Neratinib for HER2. Molecular dynamic simulation of EGFR and HER2 lead complexes ensure the ligand's appropriate refinement in the dynamic system. The target and ligand complex interaction motif established a high affinity of lead candidates in a dynamic system similar to molecular docking results. This study reveals that Panaxadiol hit molecule can be developed as a novel multi-target EGFR and HER2 target inhibitor with greater potential and low toxicity.Communicated by Ramaswamy H. Sarma.

Exploration and evaluation of bioactive phytocompounds against BRCA proteins by in silico approach.

The proteins encoded by the two major breast cancer genes (BRCA1 and BRCA2), ensure the stability of DNA and prevent uncontrolled cell growth; mutation of these genes is linked to the development of hereditary breast cancers. Exploration of human breast cancer inhibitors plays a vital role in the drug discovery process. In the current work, in silico studies were performed which involves a computational approach for the identification of active phytocompounds from the diverse set of medicinal plant products against the BRCA receptor. The in silico study through pharmacokinetics and pharmacodynamics properties shown promising outcomes for these phytocompounds data set as breast cancer inhibitors. It was observed that the compounds conformed to the Lipinski's rule of five and had good bioavailability. The drug-likeness model score and ADMET profile of the designed ligands also established their potential as a drug candidate. The docking study provided useful insights on potential target-lead interactions and indicated that the newly designed leads had a good binding affinity for BRCA targets. A pharmacophore model was built to explore the scaffolds for BRCA inhibitory activity. An effort is made to screen an inhibitor against BRCA targets by combining the use of ADMET, docking score, and pharmacophore model.Communicated by Ramaswamy H. Sarma.