Epidermal growth factor receptor (EGFR) enhances lung cancer development, due to their inability to permeate the cell membrane, secreted growth factors work through specialized signal transduction pathways. The purpose of this study is to find out a novel anticancer agent that inhibits EGFR and reduces the chances of lung cancer. A series of triazole-substituted quinazoline hybrid compounds were designed by Chemdraw software and docked against five different crystallographic EGFR tyrosine kinase domain (TKD). For docking and visualization PyRx, Autodock vina, and Discovery studio visualizer were used. Molecule-14, Molecule-16, Molecule-19, Molecule-20, and Molecule-38 showed significant affinity but Molecule-19 showed excellent binding affinity (−12.4 kcal/mol) with crystallographic EGFR tyrosine kinase. The superimposition of the co-crystalized ligand with the hit compound shows similar conformation at the active site of EGFR (PDB ID: 4HJO) indicating excellent coupling and pharmaceutically active. The hit compound showed a good bioavailability score (0.55) with no sign of carcinogenesis, mutagenesis, or reproductive toxicity properties. MD simulation and MMGBSA represent good stability and binding free energy demonstrating that the hit (Molecule-19) may be used as a lead compound. Molecule-19 also showed good ADME properties, bioavailability scores, and synthetic accessibility with fewer signs of toxicity. It was observed that Molecule-19 may be a novel and potential inhibitor against EGFR with fewer side effects than the reference molecule. Additionally, the molecular dynamics simulation revealed the stable nature of protein-ligand interaction and provided information about the amino acid residues involved in binding. Overall, this study led to the identification of potential EGFR inhibitors with favorable pharmacokinetic properties. We believe that the outcome of this study can help to develop more potent drug-like molecules to tackle human lung cancer. Graphical Abstract Communicated by Ramaswamy H. Sarma

A biocatalyst is an enzyme that speeds up or slows down the rate at which a chemical reaction occurs and speeds up certain processes by 10⁸ times. It is used as an anticancer agent because it targets drug activation inside the tumor microenvironment while limiting damage to healthy cells. Biocatalysts have been used for the synthesis of different heterocyclic compounds and is also used in the nano drug delivery systems. The use of nano-biocatalysts for tumor-targeted delivery not only aids in tumor invasion, angiogenesis, and mutagenesis, but also provides information on the expression and activity of many markers related to the microenvironment. Iosmapinol, moclobemide, cinepazide, lysine dioxygenase, epothilone, 1-homophenylalanine, and many more are only some of the anticancer medicines that have been synthesised using biocatalysts. In this review, we have highlighted the application of biocatalysts in cancer therapies as well as the use of biocatalysts in the synthesis of drugs and drug-delivery systems in the tumor microenvironment.

The main objective of this present study was to analyze the anti-inflammatory activity of the compound 1- 3- [3-(substituted phenyl) prop-2-enoyl) phenyl thiourea against inflammation receptors Secretory Phospholipase A2 (sPLA2-X), Cyclooxygenase-2 (COX-2), Interleukin-1 Receptor-associated Kinase 4 (IRAK4), Tumor Necrosis Factor (TNF-alpha) and Inducible Nitric Oxide Synthase 4 using various in-silico techniques. The 3D structures of the receptors were retrieved from Protein Data Bank in PDB format. The ligand molecule was sketched in Chemdraw Ultra v 10.0. The proteins and the ligand molecule were then individually prepared for docking using AutoDock Tools. Docking was performed using AutoDock Vina. Swiss-ADME and Pre-ADMET web servers were used for ADME, drug-likeness, and toxicity analysis. The receptor showing the best binding affinity with our ligand molecule was further analyzed via Molecular Dynamics (MD) Simulations using iMODS web server. The docking results revealed that our ligand molecule showed the best binding affinity with receptor sPLA2-X. The ADME analysis results of our ligand molecule were also good. MD Simulations study showed good results with our ligand- sPLA2-X receptor docked complex. This study revealed that our ligand molecule is a significant inhibitor sPLA2-X and can be further used as a potential therapy against inflammatory disorders.