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An efficient and practical method for the series of 4‐aminoquinoline derivatives has been developed via Tin (lV) chloride catalyzed cascade cyclization from 2‐aminobenzonitrile and different acetophenones. These novel chemical entities were characterized by their 1HNMR, 13CNMR spectra and high‐resolution mass spectrometer (HRMS) with their docking studies were performed to identify potential inhibitors of Myt1kinase protein. The synthesized analogs 3a–3l were docked with Myt1 kinase protein. Among these 3c, 3f, and 3g were showing promising Glide score, prime‐MMGBSA and ADME properties similar to Neratinib, Pelitinib cancer inhibiting drugs of Myt1 kinase protein. The amino acid ASP251of Myt1 kinase protein was consistently binding to novel chemical entities and existing drugs, indicating that the amino acid is crucial and responsible for its inhibition. Docking studies revealed that the compounds 3c, 3f, and 3g indicates that they can act as strong inhibitors of Myt1 kinase protein as that of comparable existing drugs Neratinib, Pelitinib.

Protein arginine methyltransferase 5 (PRMT5) is a member of the methyltransferases family, a type II arginine enzyme that is crucial for many cellular processes and is associated with many cancer diseases. In this study, pharmacophore-based 3D QSAR modeling, virtual screening and binding free energy studies were carried out from a set of 61 potent compounds reported being inhibitors of PRMT5 protein. A five-point pharmacophore model (AADHR) was generated and this model is used to generate an atom-based 3-Dimensional quantitative structure-activity relationship (3D-QSAR). The obtained 3D-QSAR model has high correlation coefficient (R2 = 0.91), cross-validation coefficient (Q2 = 0.82), F value (140.3), low RMSE (0.47) and pearson R-value (0.91). A library of 329825 molecules (ChEMBL database) is screened with pharmacophore model to retrieve hit molecules that are further subjected for molecular docking to identify best fit-active conformations binding at the receptor site of PRMT5 protein. Further, we are calculated ADME and toxicity properties using QikProp module and pkCSM server and finally prioritized the lead molecules by binding free energy prediction.