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In this study, eighteen new ligands (B1–B18) containing a thiosemicarbazide core were synthesized and characterized in terms of physicochemical properties, molecular docking and in vitro biological activity. The structures of eleven ligands were investigated using X-Ray diffraction and Hirschfeld Surface analysis. To study the structure-activity relationship, the organic ligands contained pyridin-2-ylmethyl, pyridin-3-ylmethyl or pyridin-4-ylmethyl moieties and various substituents. Their pharmakokinetic profiles and molecular docking results suggest high potential as new drug candidates. The complexing ability of the selected organic ligands was also evaluated, yielding five new Cu(II) complexes (Cu(B1)Cl 2 , Cu(B4)Cl 2 , Cu(B10)Cl 2 , Cu(B17)Cl 2 , Cu(B18)Cl 2). The obtained results suggest the formation of the polymeric structures. All organic ligands and Cu(II) complexes were tested for anticancer activity against prostate and melanoma cancer cells (PC-3, DU-145, LNCaP, A375, G-361, SK-MEL-28) and normal fibroblasts (BJ), as well as antimicrobial activity against six selected bateria strains. Among B1–B18 compounds, B3 , B5 , B9 , B10 , B12 and B14 exhibited cytotoxic activity. The studied Cu(II) complexes were in general more active, with Cu(B1)Cl 2 exhibiting antincancer activity agains all three prostate cancer cells and Cu(B10)Cl 2 reaching the IC 50 value equal to 88 μM against G-361 melanoma cells. Several compounds also exhibited antimicrobial activity against gram-positive and gram-negative bacteria. It was found that the type of specific substituents, especially the presence of -chloro and -dichloro substituents had a greated impact on the cytotoxicity than the position of the nitrogen atom in the pyridylacetyl moiety. [Display omitted] • Synthesis of eighteen new pyridylacetyl derivatives based on the thiosemicarbazide core and five new Cu(II) complexes. • In silico biological potential predictions of the synthesized ligands. • In vitro biological activity and structure-activity relationship, including complexation impact on the biological activity.. • Compounds were studied using: X-ray diffraction, spectroscopic techniques, thermogravimetric analysis, cyclic voltammetry. [ABSTRACT FROM AUTHOR]

A column, solid phase extraction (SPE), preconcentration method was developed for determination of silver by using alumina coated with 1-((5-nitrofuran-2-yl)methylene)thiosemicarbazide and determination by flame atomic absorption spectrometry. The separation/preconcentration conditions for the quantitative recovery were investigated. At pH 2, the maximum sorption capacity of Ag+was 7.5 mg g−1. The linearity was maintained in the concentration range of 0.02–11.0 µg mL−1in the final solution or 0.14–1.10 × 104 ng mL−1in the original solution for silver. The preconcentration factor of 140 and relative standard deviation of ±1.4% was obtained, under optimum conditions. The limit of detection (LOD) was calculated as 0.112 ng mL−1, based on 3σbl/m (n = 8) in the original solutions. The proposed method was successfully applied to the determination trace amounts of silver in the environmental samples such as tea, rice and wheat flour, mint, and real water samples. [ABSTRACT FROM AUTHOR]

The preliminary cytotoxic effect of 4-ethoxycarbonylmethyl-1-(piperidin-4-ylcarbonyl)-thiosemicarbazide hydrochloride ( 1)-a potent topoisomerase II inhibitor-was measured using a MTT assay. It was found that the compound decreased the number of viable cells in both estrogen receptor-positive MCF-7 and estrogen receptor-negative MDA-MB-231breast cancer cells, with IC values of 146 ± 2 and 132 ± 2 μM, respectively. To clarify the molecular basis of the inhibitory action of 1, molecular docking studies were carried out. The results suggest that 1 targets the ATP binding pocket. [Figure not available: see fulltext.] [ABSTRACT FROM AUTHOR]

The in vitro antifungal potency of six series of 4-arylthiosemicarbazides was evaluated. Two isoquinoline derivatives with an ortho-methoxy or ortho-methyl group at the phenyl ring were the most potent antifungal agents. Molecular modeling studies and docking of all 4-arylthiosemicarbazides into the active sites of sterol 14α-demethylase (CYP51), topoisomerase II (topo II), l-glutamine: d-fructose-6-phosphate amidotransferase (GlcN-6-P), secreted aspartic proteinase (SAP), N-myristoyltransferase (NMT), and UDP-N-acetylmuramoyl- l-alanine: d-glutamate ligase (MurD) indicated the importance of both structural and electronic factors in ligand recognition and thus for the antifungal effectiveness of 4-arylthiosemicarbazides. A possible antifungal target was identified (NMT) and isoquinoline-thiosemicarbazides showed more favorable affinity than the native ligand. [Figure not available: see fulltext.] [ABSTRACT FROM AUTHOR]

4-Benzoyl-1-(4-methyl-imidazol-5-yl)-carbonylthiosemicarbazide ( 1) was synthesized, and its antibacterial and type IIA topoisomerase (DNA gyrase and topoisomerase IV) activity evaluated. ( 1) was found to have high therapeutic potential against opportunistic Gram-positive bacteria, and inhibitory activity against topoisomerase IV (IC = 90 μM) but not against DNA gyrase. An increase in activity against topoisomerase IV (IC = 14 μM) was observed when the imidazole moiety of ( 1) was replaced with the indole group in 4-benzoyl-1-(indol-2-yl)-carbonylthiosemicarbazide ( 2). However, ( 2) showed only weak antibacterial activity. Although the results of the bacterial type IIA topoisomerases inhibition study did not parallel antibacterial activities, our observations strongly imply that a 4-benzoylthiosemicarbazide scaffold can be developed into an efficient Gram-positive antibacterial targeting topoisomerase IV. The difference in activity against type IIA topoisomerases between ( 1) and ( 2) was further investigated by docking studies, which suggested that these compounds target the ATP binding pocket. [ABSTRACT FROM AUTHOR]