Synthesis, Characterization, and DNA-Binding Kinetics of New Pd(II) and Pt(II) Thiosemicarbazone Complexes: Spectral, Structural, and Anticancer Evaluation

Abstract

In a bid to come up with potential anticancer agents, a class of thiosemicarbazone ligands bearing substituted thiophene were synthesized followed by complexation with various Pd(II) and Pt(II) metal precursors. The ligands (E)-1-((thiophen-2-yl)methylene)thiosemicarbazide (L1), (E)-1-((4-bromothiophen-2-yl)methylene)thiosemicarbazide (L2), and (E)-1-((5-bromothiophen-2-yl)methylene)thiosemicarbazide (L3) were synthesized by condensation reactions and obtained in good yields. Complexation of L1 and L2 with Pd(cod)Cl2 gave C1 (C6H7Cl2N3PdS2) and C2 (C6H6BrCl2N3PdS2), respectively. Complexation of L1 with K2PtCl4 gave C3 (C6H7Cl2N3PtS2), while L3 with K2PtCl2[(PPh)3]2 gave C4 (C24H21BrClN3PPtS2). The structures and coordination for all compounds were established by FTIR, 1H-NMR, 13C-NMR, UV-Vis, elemental analysis, and single-crystal X-ray diffraction studies for ligand L1. Tuning of the spectral and anticancer activity of the compounds was investigated by changing the position of the bromide substituent, metal center, and the σ or π-donor/acceptor strength of the groups surrounding the metal center. The compounds had low to moderate anticancer potency with their spectral and structural properties correlating with the corresponding anticancer activity profiles. DNA binding modes were studied by spectroscopy and were comparable to known DNA intercalators. Structure-activity profiles were evident especially between C1 and C2 differing by the presence of a Br in position 5 of thiophene ring, which caused a remarkable increase in IC50 values, from 14.71 ± 0.016 (C1) to 43.08 ± 0.001(C2) in Caco-2 cells, 1.973 ± 0.048 (C1) to 59.56 ± 0.010 (C2) in MCF-7 cells, 16.65 ± 0.051 (C1) to 72.25 ± 0.003 (C2) in HeLa cells, 14.64 ± 0.037 (C1) to 94.34 ± 0.003 (C2) in HepG2, and 14.05 ± 0.042 (C1) to >100(C2) in PC-3 cells.

Single crystal, Hirshfeld surface, DFT analyses of (E)‐2‐(2‐chloro‐6‐fluorobenzylidene)hydrazinecarbothioamide: Elastase inhibition and DNA binding studies

“…This comparison as given in Table 8 further indicated that compound 3 binds significantly with ds‐DNA. [ 11,49–55 ] In comparison with our previously reported work, [ 11 ] in present studies, the binding constant was evaluated 10 order of magnitude higher for compound 3 . The reason of comparatively stronger binding could be attributed to the presence of chlorine in the structure.…”

Silver(I) pyridinyl complexes with benzothiazole, thiophene, and furan moieties: DNA/protein‐binding, antibacterial, antioxidant, and anticancer studies

“…This decreases the probable transitions, and the effect is observed as a hypochromic shift. [ 43,44 ] To estimate the binding affinity of L 1 ‒L 3 and 1‒9 toward CT‐DNA, the intrinsic binding constant K b was calculated using the Wolfe‐Shimer equation (Equation ) by determining the ratio of the slope to the intercept from the plot of [DNA]/( ε a – ε f ) versus [DNA]. $$$\frac{[\mathrm{DNA}]}{{\varepsilon }_{{\rm{a}}}-{\varepsilon }_{{\rm{f}}}}=\frac{[\mathrm{DNA}]}{{\varepsilon }_{{\rm{b}}}-{\varepsilon }_{{\rm{f}}}}+\frac{1}{{K}_{{\rm{b}}}}{\varepsilon }_{{\rm{b}}}-{\varepsilon }_{{\rm{f}}},$$$where [DNA] is the concentration of the CT‐DNA, ε a , ε b , and ε f are apparent, fully bound complex, and free complex extinction coefficients, respectively.…”

“…[39][40][41][42] T A B L E 3 Mean ± standard deviation values of in vitro antioxidant activities of L 1 -L shift. [43,44] To estimate the binding affinity of L 1 -L 3 and 1-9…”

Role of the auxiliary ligand in determining the genotoxicity and mode of cell death of thiosemicarbazone Pd(ii) complexes

“…51 Through noncovalent interactions such as groove and intercalation modes, certain thiosemicarbazone Pd complexes exhibit weak binding to DNA. 52,53 Their cytotoxic effects are not countered by the low preference for DNA. Without preferential DNA binding, other Pd targets, such as topoisomerase I and II, which have a positive correlation with colon cancer, are highly effective at causing cell death.…”