Anticancer activity

The objective of the present work was the synthesis of 1-[5-acetyl-4 (4-substituted phenyl)-2,6-dimethyl-1,4-dihydroxypyridine-3-yl]-ethan-1-one and evaluation of in vitro anticancer activity. Based on this a new series of compound had been planned to synthesize by reacting acetyl acetone with various aromatic aldehydes in the presence of ammonium acetate. The in vitro anticancer activities were carried out against Human small cell lung DMS 114 cell line and Human colon cancer cell line HCC 2998 and MTT assay was used to analyze the cell growth inhibition of the both. The results had been displayed that compound B1-B4 were possessed an excellent anticancer activity (at 25 µg/ml) against both Human small cell lung DMS 114 cancer cell line and Human colon cancer cell line HCC 2998 and doxorubicin (at 10µg/ml) was used as a standard drug for Human small cell lung DMS 114 cancer cell line and 5-Fluro uracil (5-FU) for Human colon cancer cell line HCC 2998. In the present study IC50  values below 4 µg/ml were displayed by the  compound B1 (IC50 of 4.0 µg/ml), B2 (IC50 of 3.4 µg/ml), B3 (IC50 of 3.2 µg/ml) and  B4 (IC50 of 3.1 µg/ml) against Human  small cell lung DMS 114 cancer cell line and  B1( IC50 of 3.5 µg/ml), B2 (IC50 of 3.2 µg/ml), B3 (IC50 of 2.9 µg/ml) and B4 (IC50 of 2.9 µg/ml) against Human colon cancer cell line HCC 2998. The IC50 values of standard drugs doxorubicin and 5-FU were found to be 1. 2 µg/ml and 1.1 µg/ml.

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. Cyclin-dependent kinase 2 (CDK2) is a member of a highly conserved family of protein kinases that regulate the eukaryotic cell cycle. Tumour-associated 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 tumour 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.