New anticancer zinc(II) complexes comprising thiosemicarbazones of saturated ring: structure, DNA/protein binding, DNA cleavage, topoisomerase-1 inhibition and anti-proliferation studies

The reaction of the thiosemicarbazones (CH2)(4)C=NN(H)C(=S)NHR (R = H, Me) with zinc(II) acetate in methanolic solution proceeds readily under mild conditions to form stable mononuclear complexes Zn[(CH2)(4)C=NN=C(S)NHR](2). DNA interaction studies show that the zinc(II) complexes bind to DNA via groove mode and exhibit efficient DNA cleavage activity in the presence of hydrogen peroxide. Also, the complexes display a binding affinity to bovine serum albumin protein with K-BSA values of ca 10(5) M-1. Topoisomerase catalytic inhibition studies suggest that both complexes are efficient topoisomerase-I impeders. Furthermore, the anti-proliferative effects of the two complexes on five human tumor cell lines (Caki-2, MCF-7, CaSki, NCI-H322M and Co-115) indicate that both complexes have the potential to act as effective anticancer drugs. Copyright (C) 2016 John Wiley & Sons, Ltd.