Design, synthesis, docking studies and biological evaluation of novel 2-(1- isonicotinoyl-3-phenyl-1H-pyrazol-4-yl)-3-phenylthiazolidin-4-one derivatives as novel anticancer agents with Aurora-A Kinase inhibition

Abstract

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, docking studies, and biological evaluation of novel 2-(1-isonicotinoyl-3-phenyl-1H-pyrazol-4-yl)-3-phenylthiazolidin-4-one derivatives as novel anticancer agents with Aurora-A Kinase inhibition.Method A total of 21 Pyrazole derivatives P (1-21) were synthesized by using the Vilsmeier Haack reagent which was characterized by FT-IR, 1H NMR, 13C NMR and Mass spectroscopy. The synthesized derivatives were evaluated for their potential in vitro anticancer activity and Aurora A kinase inhibitory activity.Results The cytotoxicity assay (MTT assay) showed that compound P-6 exhibited potent cytotoxicity (IC50 = 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 IC50 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, docking studies, and evaluated for their in vitro anticancer activity by MTT assay and Aurora A kinase inhibitory activity. The results established that P-6 is a prospective aspirant for the development of anticancer agents targeting Aurora-A kinase.