Salicylaldehyde thiosemicarbazone copper complexes: impact of hybridization with estrone on cytotoxicity, solution stability and redox activity

Abstract

<p>Copper complex of a novel estrone–thiosemicarbazone hybrid with significant cytotoxicity, lipophilicity and solution stability in addition to its structurally related bicyclic analogue.</p>

Solution Equilibrium Studies on Salicylidene Aminoguanidine Schiff Base Metal Complexes: Impact of the Hybridization with L-Proline on Stability, Redox Activity and Cytotoxicity

“…Distribution coefficients (logD 7.4 ) were determined for the aminoguanidine ligands by n -octanol/water partitioning at pH 7.4 ( Table 1 , Figure S5 ). The obtained data for SISC (+0.83) and Pro-SISC-Me (−0.88) are lower than those of STSC (+1.59 [ 24 ]) and SSC (+0.94 [ 23 ]) due to the presence of the partly positively charged aminoguanidinium moiety and the zwitter ionic amino acid residue in Pro-SISC-Me. Based on these data, the incorporation of the proline residue resulted in a much stronger hydrophilic character as it was also observed e.g., for the proline hybrids of STSC [ 27 ], 2-formylpyridine TSC [ 30 ] or 8-hydroxyquinolines [ 33 ].…”

“…These individual spectra show that both deprotonation steps are accompanied by a significant red shift, especially in the case of the HL → L − process. The increased λ max has often originated from a more extended conjugated π-electron system, which is typically observed for the deprotonation of phenolic OH groups [ 22 , 24 ]. Notably, the deprotonation of the nonchromophoric proline moieties in Pro-SISC-Me (COOH, N Pro H + ) is not expected to result in significant spectral changes.…”

“…The salicylaldehyde semicarbazone (or salicylidene aminoguanidine, SSC, Scheme 1 ) with (O,N,O) donor set is also a non-cytotoxic compound [ 23 ]. Meanwhile, the Cu(II) complexes, both STSC and SSC, are reported to have moderate cytotoxicity [ 24 , 25 , 26 ].…”

Synthesis and conversion of primary and secondary 2-aminoestradiols into A-ring-integrated benzoxazolone hybrids and their in vitro anticancer activity

“…11 Decreased affinity to the target protein, due to electronic and steric reasons, has also been demonstrated for a number of 2-substituted estradiol derivatives (e.g., 2-methoxyestradiol), which, however, are effective in inhibiting the proliferation of various human cancer cells. [12][13][14][15][16] Although the cytotoxic effect of 2-nitroestradiol obtained by direct nitration of estradiol was weaker than that of 2methoxyestradiol, the attachment of a piperidine or morpholine ring to the phenolic-O through a spacer led to particularly potent cytotoxic compounds. 17 Interestingly, there are very few examples in the literature for the preparation of A-ring-modied estrane-based derivatives containing a [2,3]-fused heterocyclic moiety.…”

Binding Models of Copper(II) Thiosemicarbazone Complexes with Human Serum Albumin: A Speciation Study

“…Numerous metal complexes of TSCs were developed and tested as potential anticancer agents, and copper(II) complexes gained a special interest since they often exhibit higher cytotoxicity, compared to their corresponding ligands [ 9 , 10 , 11 , 12 , 13 , 14 ]. Both Triapine and STSC form highly stable and redox-active complexes with copper(II) [ 15 , 16 , 17 , 18 ], and X-ray crystallography studies showed that the metal ion adopts a square planar coordination geometry with the tridentate binding of the TSC ligand and a chlorido co-ligand (or water) [ 9 , 18 , 19 ]. Based on the solution stability and structural studies, complexes with {N,N,S − } and {O − ,N,S − } coordination modes predominate at physiological pH in the case of Triapine and STSC, respectively [ 15 , 16 ].…”