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
