Abstract
Microtubule affinity-regulating kinase 4 (MARK4) is a potential drug target as the same is found to be over expressed in several types of cancers. In search of effective MARK4 inhibitors, we have synthesized and characterized Isatin-triazole hydrazones (9a-i) and evaluated their inhibitory potential. Of all the compounds, 9g showed better binding affinity and enzyme inhibition potential in sub micromolar range. Human serum albumin (HSA) binding assay suggested an easy transportation of 9g in blood stream due to its binding affinity. In vitro anticancer studies performed on MCF-7, MDA-MB-435s and HepG2 cells using 9g showed inhibition of cell proliferation and cell migration. Further, 9g induces apoptosis in these cancerous cells, with IC50 values of 6.22, 9.94 and 8.14 μM, respectively. Putatively, 9g seems to cause oxidative stress resulting in apoptosis. Functional assay of 9g with a panel of 26 kinases showed MARK4 specific profile. In conclusion, 9g seems to possess an effective inhibitory potential towards MARK4 adding an additional repertoire to anticancer therapeutics.
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•A series of Isatin-triazole hydrazones were designed and synthesized as MARK4 inhibitors.•Compound 9g showed better binding affinity and enzyme inhibition potential in sub micromolar range.•Isothermal titration calorimetry (ITC) suggested an easy transportation of 9g in blood stream due to its binding affinity towards HSA.•9g inhibited cell proliferation, cell migration and induces apoptosis in cancerous cells.•9g with commercially available panel of 26 kinases showed MARK4 specific profile.