Aromatic Thiosemicarbazones Research Articles

Bismuth(III) halide complexes of aromatic thiosemicarbazones: Synthesis, structural characterization and biological evaluation

Four new bismuth(III) thiosemicarbazone complexes, {BiCl3(η1-S-Hacptsc)3} (1), {[BiBr3(η1-S-Hacptsc)3]·CH3OH} (2), {[BiI2(µ2-I](η1-S-Hacptsc)]2} (3) and {[BiCl2(µ2-Cl)(η1-S-Hbztsc)2]2} (4), were prepared with the ligands acetophenone thiosemicarbazone (Hacptsc) and benzaldehyde thiosemicarbazone (Hbztsc). The complexes were characterized by a series of spectroscopic techniques. The crystal structures of 1–4 were also determined by X-ray diffraction. To the best of our knowledge, complexes 1–4 are the first examples of bismuth(III) halide aromatic thiosemicarbazones. Hirshfeld surface analysis studies show that H…H and X…H/H…X interactions of complexes 1–4 play an important role in the formation of supramolecular aggregation. Complexes 1–4 have been tested for their in vitro cytotoxic activity against human breast adenocarcinoma (MCF-7) cells. The toxicity of 1–4 has been evaluated on normal human fetal lung fibroblast cells (MRC-5). Complexes 1–4 appeared to show low cytotoxic activity and low toxicity. The antibacterial activity of 1–4 and their ligands was evaluated against the Gram negative species Pseudomonas aeruginosa (P. aeruginosa) and Escherichia coli (E. coli) and Gram positive ones Staphylococcus epidermidis (S. epidermidis) and Staphylococcus aureus (S. aureus) by the Inhibition Zone (IZ) method. The influence of 1–4 on the catalytic peroxidation of linoleic acid by the enzyme lipoxygenase (LOX) has been determined experimentally. The IC50 values reveal that the synthesized bismuth(III) aromatic thiosemicarbazone complexes have good potential to inhibit lipoxygenase, with values better than the free aromatic thiosemicarbazone ligands and cisplatin.

Halogenated aromatic thiosemicarbazones as potent inhibitors of tyrosinase and melanogenesis.

A set of 21 halogenated thiosemicarbazones (TSCs) have been synthesized and its inhibitory properties toward activity diphenolase of mushroom tyrosinase and their ability to inhibition of melanogenesis in B16F10 murine, melanoma cell line have been investigated. The molecular docking to the active site of the enzyme has been also performed to investigate the nature of enzyme-inhibitor interactions. The obtained outcomes allowed us to perform SAR analysis. TSC 6, 12 and 21 exhibited the most potent inhibitory properties showing IC50 of 0.5, 0.9 and 0.8 µM, respectively. They revealed reversible and competitive manner of tyrosinase inhibition. According to SAR analysis, para-substituted acetophenone derivatives of thiosemicarbazones have the highest affinity to the enzyme among the investigated compounds. Melanin production in B16F10 cells was inhibited by all investigated compounds at the micromolar level. Suggested inhibition mechanism is based on the interaction between a sulfur atom of thiourea moiety of the thiosemicarbazones, and copper ions in the active site of the enzyme. These results might be useful in searching novel inhibitors of melanogenesis which could be used in the cosmetic and food industry.

Synthesis, Biological Evaluation and Ligand Based Pharmacophore Modeling of New Aromatic Thiosemicarbazones as Potential Anticancer Agents.

Two series of new aromatic thiosemicarbazone derivatives were synthesized by condensation of N-(4-cyanophenyl)hydrazine carbothioamide (I) and N-(4-methylsulfanylphenyl)hydrazine carbothioamide (II) with appropriate aromatic aldehydes in order to investigate their antiviral and cytostatic potency. The chemical structures of all compounds were fully characterized by elemental analysis and spectroscopic techniques. The results of the bioassays indicated that compounds Id, Ie, If and IIf proved inhibitory against influenza virus A (EC50 = 13 – 27 μg/mL for strain H1N1 and 9.3 – 18 μg/mL for strain H3N2). Compounds Ig and IIg were the most cytostatic compounds with inhibition of HeLa cell proliferation at an IC50 = 0.3 μg/mL for Ig and 1.9 μg/mL for IIg. Especially, compound Ig showed the highest cytostatic activity with IC50 of 0.30, 0.70 and 2.50 μg/mL against HeLa, CEM and L1210 cell lines, respectively. This inhibition range was within the same order of magnitude as that for cisplatin. Furthermore, molecular modeling was carried out to examine the cytostatic activity and determine the best pharmacophore model as a guide for the design and development of potential prodrugs in future studies.

Inhibitory properties of aromatic thiosemicarbazones on mushroom tyrosinase: Synthesis, kinetic studies, molecular docking and effectiveness in melanogenesis inhibition

The group of 19 thiosemicarbazones (TSCs) were synthesized and its inhibitory activity toward mushroom tyrosinase and ability to inhibition of melanogenesis in B16 cells were investigated. Moreover, molecular docking of these compounds to the active site of the enzyme was performed. The obtained results allowed to make the structure-activity relationship (SAR) analysis. Kinetic studies revealed that TSCs 1, 2, 11 and 18 have better inhibitory properties than kojic acid, a reference compound, with the best inhibitory constant (Ki) value of 0.38 µM for TSC 2. According to SAR analysis, the smaller and less branched molecules exhibit higher affinity to the enzyme. Melanin production in B16 cells was inhibited by all investigated compounds at micromolar level. Most of compounds studied in this work can be considered as potent inhibitors of tyrosinase and melanogenesis. They may have broad application in food preservatives and cosmetics. Combined results of molecular docking and SAR analysis can be helpful in designing novel tyrosinase inhibitors of desired properties.

Microwave assisted synthesis, X-ray crystallography and DFT calculations of selected aromatic thiosemicarbazones

Series of four benzaldehyde thiosemicarbazones has been synthesized under microwave irradiation and characterized structurally by means of infrared and NMR spectroscopies and mass spectrometry. Their crystal structures were determined by single crystal X-ray analysis followed by DFT calculations. Partial charges on the molecular surface and dipole moments of the structures were calculated. Crystal structures are stabilized by intramolecular hydrogen bonding and stacking interactions. Studied compounds are interesting as antiproliferative and antifungal agents acting through interactions with iron. Thus presented results may be useful in design new more active or specific structures.

Aromatic thiosemicarbazones, their antiviral action and interferon. 1. The decreasing of adenovirus type 1 resistance against interferon by methisazone in vitro

The mechanism of N-methyl-izat in-thiocarbazone (methisazone, Mel ВТ) antiviral activity has been studied on Ad 1-infected HEp2 and HeLa cells. Mel ВТ did not induce interferon and did not directly inhibit viral and cell translation. The adenoviral infection was not affected by recombinant human interferon a2 (rIFN). Mel ВТ showed antiviral effect in AdI-infected HEp2 or HeLa cells when rIFN had added to HeLa cells or in the period of interferon induction during virus infection (in HEp2 cells). In the presence of this compound, the El A transcription was unchanged in infected cells as compared to untreated control, while early transcription was decreased, the beginning of viral replication being retarded. Futhermore, the VAI RNA synthesis was also greatly suppressed. These effects were independent on interferon treatment and disappeared when MeIВТ had been added during the late phase of virus growth cycle. Actually, MeIВТ can induce the delay of VAI RNA transcription promoting interferon antiviral effect

THE PREPARATION OF SOME THIOSEMICARBAZONES CONTAINING THE s-TRIAZINE RING

The reaction between cyanuric chloride and aliphatic thiosemicarbazones results in the formation of 1:1 adducts containing a dichloro-s-triazine ring. Chemical evidence, infrared spectroscopy, and microbiological studies indicate that the addition of the triazine ring takes place at the N2 atom of thiosemicarbazones. Since cyanuric chloride failed to react similarly with aromatic thiosemicarbazones, a different type of condensation product was obtained by another method, in which cyanuric chloride was first condensed with o-, or p-hydroxybenzaldehyde to give 1:3 adducts containing free carbonyl groups. Reaction of these compounds with thiosemicarbazide gave the corresponding tri-thiosemicarbazones.

ペンタシアノ鉄錯塩による芳香族第一級アミン及び若干の有機硫黄化合体の呈色反応について

The pentacyano-iron complex salts, such as sodium nitroprusside, sodium pentacyano-amminferroate and sodium pentacyanoaquoferroate, react with aromatic primary amines and some R-NH-CS-NH-R′ type compounds, such as aromatic thiosemicarbazones, thiocarbanilides, and p-ethoxyphenylthioureas, in caustic soda solutions, in the presence of hydrogen peroxide, to give green coloration. The procedure is as follows: To a very small amount of the sample are added 5 drops of 2.5% solution of sodium nitroprusside, 1% solution of sodium pentacyanoamminferroate or 1% solution of sodium pentacyanoaquoferroate, 2 drops of 35% hydrogen peroxide, and 3 drops of 1N sodium hydroxide, and the mixture is heated in a boiling water bath.Green coloration is also developed by reacting sodium nitroprusside and sodium azide, in the phosphoric acidity, to aromatic primary amines and R-NH-CS-NH-R′ type compounds, and rendering the mixture alkaline with sodium hydroxide. This method can also be used to estimate qualitatively the aromatic primary amines and some compounds of R-NH-CS-NH-R′ type.