Metal complexes of a pro-vitamin K3 analog phthiocol (2-hydroxy-3-methylnaphthalene-1,4-dione): synthesis, characterization, and anticancer activity
Shital Harihar, Nishigandha Mone, Surekha Satpute, Dattatray Chadar, Debamitra Chakravarty, Thomas Weyhermüller, Ray J. Butcher, Sunita Salunke‐Gawali
Abstract
coordination is observed in Mn(II) complexes (1 and its methanol adduct 1B). A Na(I) complex of phthiocol, Na(pht), is isolated as a polymer. The ligand phthiocol and the complexes Na(pht), 1, 1A, and 3 crystallize in a monoclinic crystal system. X-ray structures reveal that the bond distances of coordinated phthiocol ligands are in the reduced naphthosemiquinone form in the complexes synthesized at 0 °C. The metal complexes of phthiocol (pht) were evaluated for their anticancer activity against MCF-7 (breast) and A549 (lung) cancer cell lines. Experiments like apoptosis, mitochondrial potential, reactive oxygen species (ROS) production, effect on the cell cycle, and cell proliferation were performed to compare selected complexes against both cell lines. The metal complexes of phthiocol synthesized at 0 °C showed substantial cytotoxic activity against MCF-7 and A549 cell lines. Further, effect of selected phthiocol complexes on peripheral blood mononuclear cells (PBMCs) was adventitious to realize their safety. Vitamin K3, phthiocol, and metal complex 4 successfully inhibited the enzymatic activity of human topoisomerase II. The multifunctionality of any anticancer agent influencing apoptosis, mitochondrial dysfunction, the effect on the cell cycle, and cell proliferation is crucial for defining the prognosis and precise treatment of cancer.