Design, synthesis, anticancer evaluation and docking studies of novel 2-(1-isonicotinoyl-3-phenyl-1H-pyrazol-4-yl)-3-phenylthiazolidin-4-one derivatives as Aurora-A kinase inhibitors.

INTRODUCTION

Aurora-A kinase is associated with the Aurora kinase family which has been considered a striking anticancer target for the treatment of human cancers.

OBJECTIVE

To design, synthesize, anticancer evaluation, and docking studies of novel 2-(1-isonicotinoyl-3-phenyl-1H-pyrazol-4-yl)-3-phenylthiazolidin-4-one derivatives as Aurora-A Kinase inhibitors.

METHOD

A total of 21 Pyrazole derivatives P (1-21) were synthesized by using the Vilsmeier Haack reagent which was characterized by FT-IR, H NMR, C NMR, and Mass spectroscopy. The synthesized derivatives were evaluated for their potential in vitro anticancer activity by MTT assay and Aurora-A kinase inhibition assay.

RESULTS

The cytotoxicity assay (MTT assay) showed that compound P-6 exhibited potent cytotoxicity (IC = 0.37-0.44 μM) against two cancer (HCT 116 and MCF-7) cell lines, which were comparable to the standard compound, VX-680. Compound P-6 also showed inhibition of Aurora-A kinase with an IC value of 0.11 ± 0.03 µM. A Docking study was done to compound P-6 and P-20 into the active site of Aurora A kinase, in order to get the probable binding model for further study.

CONCLUSION

A series of 21 novel pyrazole derivatives P(1-21) were designed, synthesized, in vitro anticancer evaluation, and docking studies for Aurora A kinase inhibition. The results established that P-6 is a prospective aspirant for the development of anticancer agents targeting Aurora-A kinase.