Design synthesis characterization molecular docking of novel 4 anilino quinazolines and its in vitro anticancer antitubercular and antimicrobial property

Abstract

The current research project consist of Design Synthesis Characterization Molecular Docking of Novel 4 Anilino quinazolines and its in vitro Anti Cancer Anti Tubercular and Anti Microbial Property Novel 4 anilino Quinazoline derivatives were designed and synthesized by fragment replacement and lipophilic group insertion High yields were obtained under mild reaction condition The structure of the synthesized compounds was characterized by FTIR 1HNMR 13CNMR and Mass spectral analysis The data were in correlation with the expected structure Molecular Docking and Dynamics Simulation studies were carried out using AutoDock Tools and program 4 based on the genetic algorithm GA method and Gromacs respectively The synthesized compounds were subjected to theoretical in silico ADME prediction using Molinspiration Osiris property explorer and Swiss ADME web tool The designed molecules were docked into the active site of EGFR Tyrosine Kinase Dihydro Folate Reductase and PARP I Enzymes as Cancer target Enoyl Reductase as Tubercular target and DNA Gyrase as Microbial target Molecular Dynamics simulation study revealed that the protein EGFR tyrosine kinase PDB id 1M17 has equilibriated more when it interacts with the inhibitor SMOQ2 SNAQ3 DMUQ5 and 6AUQ6 The results of Toxicity risk assessment showed that all the compounds were found to be non-toxic ie non mutagenic non tumorigenic non irritant and does not produce any reproductive effect The bioactivity score revealed that the compounds were found to act as a ligand for various receptors like GPCR Ion channel modulator Kinase inhibitor Nuclear Receptor ligand protease inhibitor and enzyme inhibitor None of the compounds screened has violated the Lipinskis rule of five and the oral bioavailability was found to be common The synthesized compounds were evaluated