Synthesis, Characterization, and Biological Activity of Hybrid Thiosemicarbazone–Alkylthiocarbamate Metal Complexes

Abstract

A series of hybrid ligands (H 2 L 1 −H 2 L 3 ) derived from 4-methyl-3-thiosemicarbazide and hydrazinecarbothioic acid O-alkyl esters were synthesized and characterized by NMR. The ligands were chelated with copper (4−6), nickel (7−9), and zinc (10−12) and characterized by spectroscopy, electrochemistry, and single crystal X-ray crystallography. The chelated metals displayed substantial anodic shifts in the Cu II/I reduction potential of ∼160 mV relative to their bis(thiosemicarbazone) analogues. The metal chelates 4−12 were evaluated for potential anticancer activity by MTT assays, and selected results were confirmed by clonogenic and trypan blue assays. The copper derivatives 4 and 6 were found to have potent and cancer-selective antiproliferative effects, with GI 50 values less than 100 nM in A549 lung adenocarcinoma cells compared with at least 20-fold less activity in IMR90 nonmalignant lung fibroblasts. In comparison, the nickel complexes were much less active and had little cancer-selectivity. Varying by ligand, the zinc complexes were less potent or had comparable activity compared to that of the corresponding copper complex. UV−visible spectroscopy indicated that zinc complex 10 was transmetalated in the presence of equimolar copper, whereas nickel complex 7 was not. Copper complexes 4 and 6 were also assessed in the NCI60 screen and were found to have cytotoxic activity against most solid tumor cell lines. In MTT assays, 4 and 6 were substantially more active against A549 cancer cells than Cu(ATSM) and were more cancer-selective (for A549 compared to IMR-90) than Cu(GTSM). Our results suggest that hybrid thiosemicarbazone− alkylthiocarbamate copper complexes have potential for development as new anticancer agents.

Thiosemicarbazone modified zeolitic imidazolate framework (TSC-ZIF) for mercury(ii) removal from water

“…Since the linker contains a thioamide -NH-C]S functional group, it can exhibit the thione-thiol tautomerism. 71 The thiol n(S-H) band around 2570 cm À1 is absent from the IR spectra of the TSC-ZIFs, while the n(N-H) band is present at 3153 cm À1 , indicating that, in the solid-state, the linker remains as the thione tautomer. The proposed IR assignments of the ZIFs are in good agreement with literature data.…”

“…[72][73][74] The introduction of the thioamide groups in MIM 3.5 :Bisthio 1 :Zn and MIM 3.5 :Thio 1 :Zn resulted in new vibrational bands, with characteristic absorptions at 2122 cm À1 corresponding to the n as (NH-C]S) modes. 71 NMR analysis. The degree of functionalization of Ald-ZIFs and TSC-ZIFs was determined by digesting the ZIFs under acidic conditions.…”

“… 72–74 The introduction of the thioamide groups in MIM 3.5 :Bisthio 1 :Zn and MIM 3.5 :Thio 1 :Zn resulted in new vibrational bands, with characteristic absorptions at 2122 cm −1 corresponding to the ν as (NH–C S) modes. 71 …”

Fragmentation Study, Dual Anti-Bactericidal and Anti-Viral Effects and Molecular Docking of Cobalt(III) Complexes

“…In this context, thiosemicarbazones Schiff bases are a recognized class of bioactive molecules with antimicrobial and antiviral purposes [21,22]. It is well established that the complexation of thiosemicarbazone ligands to metal ions can show considerable efficacy to improve biological activity [3,7,23,24]. Furthermore, this class of ligands has shown reduced toxic effects when chelated to metal ions [23].…”

Synthesis and Antitumor Activity Evaluation of Cyclometalated 2H‐Indazole Ruthenium(II) and Iridium(III) Complexes

“…With the emergence of metallo-therapeutics several achievements were made in the field of medical research. [6,7] Interestingly, in the past two decades therapeutic stimuliresponsive (pH, enzyme, light, temperature, etc) metallo-drugs were reported. [8,9] Despite the advancements in drug research and understanding of the complex nature, cancer still remains as the major cause of death in human population.…”