SYNTHESIS AND MOLECULAR DOCKING STUDIES OF NOVEL BENZIMIDAZOLE DERIVATIVES AS HUMAN CYCLINDEPENDENT KINASE- 2 INHIBITORS
Srikanth Lingala*, Raghunandan Nerella, Sreenivas.Enaganti
ABSTRACT
We report here the synthesis and preliminary evaluation of novel
synthetic compounds in vivo and investigation of their anticancer
activities by binding to cyclin dependent kinase 2. Cyclin dependent
kinases (CDKs) are a family of proteins involved in the regulation of
cell cycle progression and attractive targets in oncology. Cyclindependent
kinase 2 (CDK2) is a member of a highly conserved family
of protein kinases that regulate the eukaryotic cell cycle. Tumorassociated
cell cycle defects are often mediated by alterations in
cyclin-dependent kinase (CDK) activity. According to current models,
mammalian CDKs are essential for driving each cell cycle phase, so
therapeutic strategies that block CDK activity are unlikely to
selectively target tumor cells. Emerging evidence suggests that tumor cells may also require
specific interphase CDKs for proliferation. Thus, selective CDK inhibition may provide
therapeutic benefit against certain human neoplasias. The X-ray structures of the CDK2
(PDB ID: 1DI8) were retrieved from protein data bank based on good Resolution (1.90) and
Ramachandran’s plot analysis. We have studied the influence of synthetic ligands on the
binding of Cyclin-dependent kinase 2 with the help of docking studies by using Accelrys
Discovery Studio2.5. The findings obtained in these studies indicate that these compounds
could be a potent anti – leukemic agent.
Keywords: Cyclin-dependent kinase 2 (CDK2), synthetic compounds, Leukemia, Anticancer activity.
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