Molecular Docking Studies of 1, 3- Thiazolidin-4-Ones as Potential Human Polo Like Kinase 1 (Plk 1) Inhibitors

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Polo-like kinase 1 (Plk1) belongs to a subfamily of Ser/ Thr protein kinases, collectively termed polo-like kinases (Plks). A growing body of evidence suggests that Plk1 plays important roles during multiple stages of M-phase progression and, as a result, in cell proliferation. In a series of preclinical studies, PLK1 has been validated as a cancer target. This has prompted many research scientists to develop selective PLK1 inhibitors for the treatment of cancer. The recent strategy employed in PLK1 inhibition involves the designing of small molecule inhibitors that targets the classical ATP-binding site of PLK1. Purpurogallin (PPG) and poloxin have been reported as inhibitors of the polo-box domain (PBD) of human polo-like kinase 1. Recently, new generation of PLK1 inhibitors targeting the second druggable domain of PLK1, the polo box domain, is currently being tested preclinically. We propose to design and develop 1, 3-thiazolidin-4-ones which could inhibit PLK1 for potent anticancer and anti-inflammatory activities. The 1, 3-thiazolidin – 4-ones could show anticancer and anti-inflammatory potential through inhibition of polo-like kinase 1 (PLK1) and cyclooxygenase-2 (COX 2) via NF-Kb (nuclear factor kappa-light- chain-enhancer of activated B cells) protein. Molecular docking of a set of ligands was performed using Vlife MDS 4.4 software. The 3D ligand protein complex structure of Polo Like Kinase 1 (2rku) was obtained from the protein database bank (RCSB-PDB) and processed for protein preparation and optimization. The computational studies suggest that aromatic group with non-polar electronegative substituents at second position and nitro-heterocycle either directly or through amide linkage at third position of the 1, 3-thiazolidin – 4-ones could result in better anticancer compound through inhibition of enzyme polo-like kinase 1.