Anticancer potential of 3-hydroxypyridine-2-carboxaldehyde N(4)-methyl and pyrrolidinylthiosemicarbazones and their Zn(II) complexes in different cancers via targeting MAPK superfamily signaling pathway

Abstract

Zinc(II) complexes of 3-hydroxy-2-formylpyridine N(4)-methylthiosemicarbazone (1) and 3-hydroxy-2-formylpyridine N(4)-pyrrolidinyl thiosemicarbazone (2) respectively have been synthesized and characterized by elemental analysis, IR, UV–Vis, 1H NMR spectroscopy and mass spectrometry. These compounds were investigated for their antiproliferative potential against PC3 (Prostate Cancer), DU145 (Prostate Cancer), A549 (Lung Cancer), A431 (skin cancer) and Hela (Cervical Cancer cell) cell lines. All the compounds showed good antiproliferative activity against the tested cell lines. However, compound HHyPyPyrd showed remarkable antiproliferative activity against PC3 cell line with an IC50 of 0.69 µM. Cell death analysis by propidium iodide staining showed significant increase in cell death of PC3 cells in a concentration dependent manner. Furthermore, cell cycle analysis showed cell cycle arrest of PC3 cells at S phase. Our study shows that compound HHyPyPyrd induces the downregulation of JNK, c-Jun and Erk.