Design and Optimization of Novel Pyrimidine-Morpholine Hybrids Through Computational Approaches for SRC Kinase Inhibitory Activity

Abstract

Src (non receptor tyrosine kinase) plays a role in multiple pathways leading to tumor survival, proliferation and metastasis. Inhibiting Src kinase would be a therapeutic benefit in Src dependent cancers. Most of the nitrogen containing heterocyclic moieties found to possess variety of biological activities. Combination of heterocyclic nucleus to active hybrids has proven to be a successful method of approach to augment biological activities. Hence a series of pyrimidine-morpholine hybrids were designed and its shape similarity studies calculated with the standard Dasatinib using Tanimoto coefficient. Designed molecules were docked with human tyrosine kinase (PDB ID: 2SRC) using AutoDock vina. Docked poses were ranked based on their binding affinities which are then compared with a reference. The studies revealed that docking of hybrid molecules with 2SRC showed promising interactions with affordable ADMET properties. The stability of highly docked complex was analyzed by molecular simulation studies and the results confirmed the docking outcomes thereby making it as a potential SRC kinase inhibitor. Hence these novel pyrimidine hybrids can be considered as lead molecules for developing novel druggable moieties for breast cancer research.

Keywords

SRC tyrosine kinase inhibition - molecular docking - shape similarity - pyrimidine-morpholine analogues

Publication History

Received: 06 January 2025

Accepted: 24 February 2025

Article published online:
17 April 2025

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