Benzaldehyde Thiosemicarbazone Research Articles

Synthesis, Characterization, and Thermal Decomposition of Antimony(III) Halide Complexes of Benzaldehyde Thiosemicarbazones

Synthesis, Characterization, and Thermal Decomposition of Antimony(III) Halide Complexes of Benzaldehyde Thiosemicarbazones

Novel alkyl-substituted 4-methoxy benzaldehyde thiosemicarbazones: Multi-target directed ligands for the treatment of Alzheimer's disease

Alzheimer's disease (AD) is a devastating neurodegenerative disorder affecting mental ability and interrupts neurocognitive functions. Treating multifactorial conditions of AD with a single-target-directed drug is highly difficult. Thus, a multi-target-directed ligand (MTDL) development strategy has been developed as a promising approach for the treatment of AD.Herein, we have synthesized two novel thiosemicarbazones as MTDLs and reported their bioactivities against diverse neuropathological events involved in AD. In vitro studies revealed that both compounds exhibited promising anticholinesterase activity (AChE, IC50 = 15.98 μM, MZET and IC50 = 30.23 μM, MZMT), well supported by a detailed computational study. Both analogs have shown good thermodynamic behaviour and stability through interactions with characteristic amino acid residues throughout simulation of 100 ns against acetylcholinesterase enzyme. In an electrophysiology assay, these analogs have shown a characteristic inhibitory response against the GluN1-1a + GluN2B subunit of N-methyl-D-aspartate receptors. Pre-treatment of BV-2 microglial cells with MZET effectively decreased nitrite production compared to nitrite produced by lipopolysaccharide-treated cells alone. Further, the effect of MZMT and MZET on autophagy regulation was determined using stably transfected SH-SY5Y neuroblastoma cells. MZET significantly enhanced the autophagy flux in neuroblastoma cells. A significant decrease in copper-catalysed oxidation of amyloid-β in presence of synthesized thiosemicarbazones was also observed.Collectively, our findings indicated that these analogs have potential as effective anti-AD candidates and can be used as a prototype to develop more safer multi-targeted anti-AD drugs.

A potentiometric and spectrofluorimetric approach to unravel inhibitory effects of semi- and thiosemicarbazones on mushroom tyrosinase activity.

The inhibitory effects on mushrooms tyrosinase activity of some semi- and thiosemicarbazones were investigated. While the semicarbazones are inactive, the thiosemicarbazones are, in general, more active than the reference (kojic acid, IC50 = 70μM), with maximum activity obtained with benzaldehyde thiosemicarbazone (IC50 = 7μM). These inhibitors probably act by coordination of the copper(II) metal ions in the active site of tyrosinase: effectively, potentiometric studies conducted in water solutions confirm that the most active thiosemicarbazone is a good ligand for copper(II) ions. The tyrosinase CD spectra do not show any significant difference by addition of an inhibitor or an inactive compound. On the contrary, interesting results were obtained by spectrofluorimetric titrations of mushrooms tyrosinase aqueous solutions with some of the investigated compounds, giving helpful information about possible mechanism of action. The thiosemicarbazones here reported are not cytotoxic on human fibroblasts and do not activate cells in a pro-inflammatory way.

NSC19723, a Thiacetazone-Like Benzaldehyde Thiosemicarbazone Improves the Efficacy of TB Drugs In Vitro and In Vivo.

The complexity and duration of tuberculosis (TB) treatment contributes to the emergence of drug resistant tuberculosis (DR-TB) and drug-associated side effects. Alternate chemotherapeutic agents are needed to shorten the time and improve efficacy of current treatment. In this study, we have assessed the antitubercular activity of NSC19723, a benzaldehyde thiosemicarbazone molecule. NSC19723 is structurally similar to thiacetazone (TAC), a second-line anti-TB drug used to treat individuals with DR-TB. NSC19723 displayed better MIC values than TAC against Mycobacterium tuberculosis and Mycobacterium bovis BCG. In our checkerboard experiments, NSC19723 displayed better profiles than TAC in combination with known first-line and recently approved drugs. Mechanistic studies revealed that NSC19723 inhibits mycolic acid biosynthesis by targeting the HadABC complex. Computational studies revealed that the binding pocket of HadAB is similarly occupied by NSC19723 and TAC. NSC19723 also improved the efficacy of isoniazid in macrophages and mouse models of infection. Cumulatively, we have identified a benzaldehyde thiosemicarbazone scaffold that improved the activity of TB drugs in liquid cultures, macrophages, and mice. IMPORTANCE Mycobacterium tuberculosis, the causative agent of TB is among the leading causes of death among infectious diseases in humans. This situation has worsened due to the failure of BCG vaccines and the increased number of cases with HIV-TB coinfections and drug-resistant strains. Another challenge in the field is the lengthy duration of therapy for drug-sensitive and -resistant TB. Here, we have deciphered the mechanism of action of NSC19723, benzaldehyde thiosemicarbazone. We show that NSC19723 targets HadABC complex and inhibits mycolic acid biosynthesis. We also show that NSC19723 enhances the activity of known drugs in liquid cultures, macrophages, and mice. We have also performed molecular docking studies to identify the interacting residues of HadAB with NSC19723. Taken together, we demonstrate that NSC19723, a benzaldehyde thiosemicarbazone, has better antitubercular activity than thiacetazone.

Novel Antimalarial Drug Screening Based on Methyl Eugenol, Cinnamaldehyde, and Thiosemicarbazone with Cysteine Protease Inhibition: In Silico Molecular Docking, Molecular Dynamics, and ADMET Studies

Plasmodium falciparum malaria contributes to significant global diseases. Computer-aided drug design, screening, and discovery were used to analyze a novel series of Methyl Eugenol Benzaldehyde Thiosemicarbazone (MEBThi) and Methyl Eugenol Cinnamaldehyde Thiosemicarbazone (MECThi) derivatives for malaria falciparum inhibition. This present study showed that 16 molecules from 28 of MEBThi and MECThi have affinities and interaction with active-site residues of cysteine protease, a key player in erythrocyte proliferation of P. falciparum. 13-MECThi demonstrates the best binding affinity at ˗8.0 kcal/mol while co-drug ˗5.6 kcal/mol. Physicochemical and pharmacokinetic assays of 13- MECThi have also revealed this potent compound. Toxicity analysis shows that 13-MECThi does not have mutagenicity and carcinogenicity characters, whereas co-drug has mutagenicity probability. The molecular dynamic evaluation illustrated that the 13-MECThi complex has higher Root Mean Square Deviation (RMSD) values, indicating its structure was more flexible than the chloroquine complex. Root Mean Square Fluctuation (RMSF) complex of receptor and 13-MECThi has no fundamental differences with chloroquine complex. This designed compound should be considered a falciparum antimalarial drug.

Green Synthesis of Ligand, Volumetric Analysis Using Micellar Medium and Antibacterial Investigations on Cu (II)-thiosemicarbazone Systems

Surfactants containing potential donor ligands can coordinate with metal ions and such compounds can beused for the removal of toxic metals and organometallic compounds from aqueous systems. Micelles haveplayed role as soil and water decontamination agents. Micellar solutions and microemulsions are efficientenvironmentally-friendly agents for cleaning artworks, especially for the selective removal of aged polymericcoatings from the surface of wall paintings. Thus micelles have great importance in chemistry. Presentwork explains the synthesis of ligand (4-(Diethylamino) benzaldehyde thiosemicarbazone) by conventionalas well as green method, volumetric analysis and antimicrobial investigations on Cu (II)- Thiosemicarbazone complexes. Solution studies on the complexes have also been carried out in different micellar (SDS, HTAB,TX-100 ) systems at 25 °C. Stability constants have been determined in 60% ethanol by pH metric study. Protonligand stability constant and metal-ligand stability have been determined potentiometrically. Antibacterialinvestigations have been carried out against, S. aureus, B.substilis bacterial strain.

One pot solvothermal synthesis of bimetallic copper iron sulfide (CuFeS2) and its use as electrode material in supercapacitor applications

This work reports one-pot solvothermal synthesis of CuFeS2 nanomaterial using Cu(NO3)2•6H2O and FeCl2(3-Cl-benztsczH)2, where benztsczH = benzaldehyde thiosemicarbazone as molecular precursors. The electrochemical performance of as-prepared chalcopyrite, CuFeS2 nanomaterial was studied in order to investigate its ability to work as a supercapacitor material for energy storage devices. The material obtained was characterized by various techniques. The XRD pattern of as-prepared chalcopyrite, CuFeS2 matches with tetragonal phase of the material (JCPDS card no. 037–0471). The crystallite size calculated using Scherrer's formula is found to be 41.5 nm. High resolution transmission electron microscopy (HRTEM) revealed the presence of nanomaterial having spherical morphology. The electrochemical properties of the as-prepared chalcopyrite, CuFeS2 electrode were investigated in aqueous electrolyte, 6 M KOH. Cyclic voltammetry (CV) and galvanostatic charge/discharge (GCD) curves show the pseudocapacitive behaviour of the CuFeS2 electrode. The material is found to have excellent specific capacitance of 206.3 C g−1 (589 F g−1) at 0.5 A g−1 current density with cycle stability of ∼82% after 2000 cycles (at current density of 4 A g−1).

Inhibition performance of halogen-substituted benzaldehyde thiosemicarbazones as corrosion inhibitors for mild steel in hydrochloric acid solution.

Halogen-substituted benzaldehyde thiosemicarbazone derivatives were synthesized and their inhibition performance for mild steel in hydrochloric acid solution were investigated systematically using weight loss measurements, electrochemical techniques, scanning electron microscopy and quantum chemical calculations. Results of weight loss measurements indicated that all these compounds exhibited excellent inhibition performance and the inhibition efficiency increased with increasing inhibitor concentrations. Polarization results revealed that the synthesized benzaldehyde thiosemicarbazone derivatives were mixed-type inhibitors. Adsorption of these compounds onto a mild steel surface was mainly chemisorption and complied with the Langmuir adsorption isotherms. Both theoretical calculations and experimental measurements suggested that the inhibition efficiency of these compounds followed the order of Br-BT > Cl-BT > F-BT > H-BT.

In silico and in vitro Antibacterial Assessment of Newly Synthesized Ni(II) Complexes of Thiosemicarbazone

Nowadays, most anti-infective agents or antibiotics are becoming resistant to several uropathogenic microorganisms. Thus, there is an urgent need of new potent candidates for treating infectious diseases and overcome the antibiotic resistance. Nickel(II) complexes of composition [Ni(Lig2)·2H2O]X2 have been synthesized with the ligand substituted benzaldehyde thiosemicarbazone (X = Cl). These obtained products were structurally interpreted by several spectroscopic studies includes FTIR for functional group detection, 1H & 13C NMR for the structural number of environment protons and carbons frame. The proposed Ni2+ complexes are octahedral structure and all ligands are coordinated with thiols or thiones and behaves as a bidentate manner. All the nickel(II) complexes were further screened in vitro antibacterial action against E. coli and S. aureus. The antibacterial activity of all the tested compounds, Ni(II) complex bearing 4-nitrobenzylidene thiosemicarbazone (4e) had shown significant inhibition against E. coli whereas overall assessment of antibacterial action indicates that all the compounds have been exhibited moderate to good inhibition growth bacterial with E. coli. Moreover, the binding affinity of the ligands had also been predicted through the molecular docking and physico-chemical properties were calculated. The synthesized nickel complexes could be more potent bacterial target inhibitor.

Synthesis and identification of meta-(4-bromobenzyloxy) benzaldehyde thiosemicarbazone (MBBOTSC) as novel ligand for cadmium extraction by ultrasound assisted-dispersive-ionic liquid-liquid micro extraction method

In this research, meta-(4-bromobenzyloxy) benzaldehyde thiosemicarbazone (MBBOTSC) as a novel ligand was synthesized from the reaction between meta-(4-bromobenzyloxy) benzaldehyde and thiosemicarbazide under basic condition in water and ethanol as solvents. Ligand has the ability to chelate ions and therefore, it was used to form a complex and extract ions. Then, the cadmium ions in water and wastewater samples were separated based on MBBOTSC by ultrasound assisted-dispersive-ionic liquid-liquid microextraction method (USA-D-ILLME) before determination by AT-F-AAS. The MBBOTSC ligand was added to the mixture of the ionic liquid/acetone (IL/AC, [OMIM][PF6]) and then injected by syringe to 50 mL of water samples at pH 6-7. The sample was put into the ultrasonic accessory for 5 minutes, after complexation (Ligand-Cd; RS…Cd….RS), the water sample was centrifuged for 3 min for phase separation. Due to complexation and back-extraction of Cd in liquid phase, the amount of Cd ions in the water samples was determined by AT-F-AAS . In optimized conditions, the Linear ranges and LOD for 50 mL of water samples were obtained 1-36 μg L-1 and 0.3 μg L-1, respectively (Mean RSD= 1.26%). The validation results were successfully achieved by spiking real samples and using ET-AAS.

Structure-Based Virtual Screening of Benzaldehyde Thiosemicarbazone Derivatives against DNA Gyrase B of Mycobacterium tuberculosis.

Emergence of antibiotic-resistant Mycobacterium tuberculosis (M. tuberculosis) restricts the availability of drugs for the treatment of tuberculosis, which leads to the increased morbidity and mortality of the disease worldwide. There are many intrinsic and extrinsic factors that have been reported for the resistance mechanism. To overcome such mechanisms, chemically synthesized benzaldehyde thiosemicarbazone derivatives were screened against M. tuberculosis to find potential inhibitor for tuberculosis. Such filtering process resulted in compound 13, compound 21, and compound 20 as the best binding energy compounds against DNA gyrase B, an important protein in the replication process. The ADMET prediction has shown the oral bioavailability of the novel compounds.

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.

Molecular docking, synthesis and anticancer activity of thiosemicarbazone derivatives against MCF-7 human breast cancer cell line

BackgroundThe aim of this study was to synthesize and evaluate anticancer activity of 2-hydroxy benzaldehyde and 4-hydroxy benzaldehyde thiosemicarbazone (2-HBTSc and 4-HBTSc) against MCF-7 breast cancer cell line. Materials and methodsThe ligands were prepared and characterized by UV vis, IR and NMR. MTT assay was used to assess viability of cells. RNA isolation, extraction and cDNA synthesis were done. Then all groups were subjected to RT-qPCR using Gene expression specific primers. Also, western blot protein expression and molecular docking were done. Two-way ANOVA with Tukey post-hoc test was employed to test the significance using GraphPad Prism. ResultsThe IC50 values were 3.36μg/ml and 3.60μg/ml for 2-HBTSc and 4-HBTSc treated MCF-7 tumor cells respectively. Tumor cell growth inhibition ranged from 38 to 49.27% in 4-HBTSc treated cells, and 19 to 25% in 2-HBTSc treated cells with increase in doses 5 μg/ml to 20 μg/ml. The protein and gene expression result showed a significant upregulation in tumor suppressor and apoptosis inducing genes while, oncogene activity was significantly downregulated. Specifically, BRCA2 and pRB gene showed the highest expression in 4-HBTSc and 2-HBTSc treated cells respectively. Conversely, RAS oncogene was downregulated significantly. Docking result showed that both 2-HBTSc and 4-HBTSc have the potential to inhibit Estrogen Receptor Alpha Ligand Binding Domain, Human 17-Beta-hydroxysteroid dehydrogenase type 1 mutant protein and Human Topoisomerase II alpha that are expressed more during Breast Cancer. ConclusionThe findings of this study imply that the test compound has potential for further study.

Ultra-fast photoreduction of toxic Cr(VI) by CdS-rGO synthesized using single source precursor

Abstract Cadmium sulfide decorated with reduced graphene oxide (CdS-rGO) nanocomposites were synthesized by CdI2(LH)2 complex [where, LH = benzaldehyde thiosemicarbazone]. Various spectroscopic and analytical techniques were used for the characterization of the cadmium complex. The solvothermal decomposition method was employed to obtain CdS-rGO using CdI2(LH)2 complex as a single-source precursor (SSP) for CdS along with graphene oxide as the precursor for rGO and ethylene glycol as a solvent. The powder X-ray diffraction study of resultant CdS-rGO nanocomposites revealed a hexagonal phase for CdS. Scanning electron microscopy shows hierarchically structured cadmium sulfide-reduced graphene oxide nanocomposites. Transmission electron microscopy images reveal CdS nanoparticles associated with reduced graphene oxide sheets to form a nanocomposite. Raman spectroscopic studies show phonon mode at 310 cm−1 associated with the hexagonal phase of CdS. the band at 1349 cm−1and 1596 cm−1 correspond to phonon modes of rGO. The CdS-rGO nanocomposites demonstrated ultra-fast reduction of toxic Cr(VI) to less toxic Cr(III) under sunlight. A plausible mechanism for photoreduction of Cr(VI) to Cr(III) using CdS-rGO under natural sunlight irradiation is proposed. The role of valence and conduction band potential with a calculated redox potential of an acceptor species and facile transfer of electrons for fast photoreduction of Cr(VI) to Cr(III) is also discussed.

Adsorption and corrosion inhibition accomplishment for thiosemicarbazone derivatives for mild steel in 1.0 M HCl medium: Electrochemical, XPS and DFT studies

Four benzaldehyde thiosemicarbazone derivatives namely as 2-benzylidene-N-phenylhydrazinecarbothioamide (L1), 2-(4-hydroxybenzylidene)-N-phenylhydrazinecarbothioamide (L2), 2-(4-chlorobenzylidene)-N-phenylhydrazinecarbothioamide (L3), and 2-(4-methylbenzylidene)-N-phenylhydrazinecarbothioamide (L4) were successfully synthesized and elucidated by physical and spectral techniques, to be specific, melting point, elemental analysis (CHNS), infrared spectroscopy (FTIR) and 1H and 13C nuclear magnetic resonance spectroscopy (NMR). These organic corrosion inhibitors behaviour for mild steel (MS) in 1.0 M HCl solution was examined using potentiodynamic polarization and electrochemical impedance spectroscopy (EIS) techniques. From the electrochemical measurements, most ligands behave as efficient inhibitors for the MS in 1.0 M HCl solution which contribute the maximum inhibition efficiency up to 93.38% for L3. The potentiodynamic polarization measurements unfolds each synthesized compound were mixed-type inhibitor based on the shifting of corrosion potentials (Ecorr) found to be lesser than ±85 mV. The electrochemical impedance spectroscopy (EIS) analysis revealed retardation of metal corrosion succeeded by cause of adsorption of the four thiosemicarbazone derivatives inhibitor molecules at the metal/solution interface. The adsorption of thiosemicarbazone molecules on the low carbon steel surface in 1.0 M HCl solution obeys Langmuir adsorption isotherm. Scanning electron microscopy (SEM) and atomic force microscopy (AFM) demonstrates in the presence of optimum concentration of L1-L4 inhibitors at 0.04 mM indicates greatly reduced surface roughness of MS in comparison with uninhibited solution. The findings were further reinforced via surface elemental analysis of metal/solution interface via X-ray Photoelectron Spectroscopy (XPS), which unveils L3 exhibit the greatest inhibition efficiency. The most plausible reason is due to benzene rings in the molecular structure increases the adsorption ability in supporting the substituent of chloro as well as conjugated double bond of C=N and C=S that chemisorbed along the surface of metal. The oxide species of FeO, Fe2O3 and FeOOH found to be chemisorbed and physisorbed on MS surface. The impact of molecular properties on the corrosion inhibition and the adsorbed sites of L1-L4 on the metal were investigated using density functional theory calculations (DFT) at the B3LYP/6–311 + G (d,p) level of theory. From the Frontier Molecular Orbitals (FMO), the Highest Occupied Molecular Orbitals (HOMO) discloses adsorption of L2 on the MS surface generally due to 2-(4-hydroxybenzylidene)-N-hydrazinecarbothioamide, whereas for L1, L3 and L4 associated to the inclusion of phenyl carbothioamide. The Lowest Occupied Molecular Orbitals (LUMOs) of L1-L4 are comparatively resembling and delocalized of all molecules. DFT reveals protonated thiosemicarbazones exhibits high correlations coefficients as up to 99–100% in comparison to the corresponding neutral forms of the molecules. The increase in the inhibition efficiency of protonated L1, L2 and L3 is proportional to the ∆N and DM.

Catalase Inhibitors with Dual Pro‐Oxidant Effect as New Therapeutic Agents in Castration‐Resistant Prostate Cancer

AbstractAlmost all patients with advanced prostate cancer (PCa) will eventually progress to incurable castration‐resistant PCa (CRPC) if endocrine therapy fails. Therefore, identifying potential cellular targets is critical for the development of novel and effective treatments for CRPC. Based on the investigation of the molecular mechanism of ATN‐224, an anticancer drug in clinical trials, in CRPC DU145 cells, the antioxidant enzyme catalase (CAT) has been recognized as an actionable CRPC therapeutic target, and the modulation of intracellular redox state through CAT inhibition has great potential for CRPC treatment. After systematic design and synthesis, the benzaldehyde thiosemicarbazone derivative BT‐1 is shown to be effective CAT inhibitor in DU145 cells. This inhibition induces the significant increase of both superoxides (O2•−) and H2O2 levels in DU145 cells. Finally, the dual pro‐oxidant effect of BT‐1 is demonstrated to lead to apoptosis as well as cell‐cycle arrest in DU145 cells, effectively reducing CRPC tumors.

Sisters in structure but different in character, some benzaldehyde and cinnamaldehyde derivatives differentially tune Aspergillus flavus secondary metabolism

Great are the expectations for a new generation of antimicrobials, and strenuous are the research efforts towards the exploration of diverse molecular scaffolds—possibly of natural origin – aimed at the synthesis of new compounds against the spread of hazardous fungi. Also high but winding are the paths leading to the definition of biological targets specifically fitting the drug’s structural characteristics. The present study is addressed to inspect differential biological behaviours of cinnamaldehyde and benzaldehyde thiosemicarbazone scaffolds, exploiting the secondary metabolism of the mycotoxigenic phytopathogen Aspergillus flavus. Interestingly, owing to modifications on the parent chemical scaffold, some thiosemicarbazones displayed an increased specificity against one or more developmental processes (conidia germination, aflatoxin biosynthesis, sclerotia production) of A. flavus biology. Through the comparative analysis of results, the ligand-based screening strategy here described has allowed us to delineate which modifications are more promising for distinct purposes: from the control of mycotoxins contamination in food and feed commodities, to the environmental management of microbial pathogens, to the investigation of specific structure–activity features for new generation drug discovery.

Thiosemicarbazone Derivatives as Inhibitors of Amyloid-β Aggregation: Effect of Metal Coordination.

Three thiosemicarbazone derivatives, namely 4-(dimethylamino)benzaldehyde 4,4-dimethylthiosemicarbazone (HL1), 4-(dimethylamino)benzaldehyde thiosemicarbazone (HL2), and 4-(dimethylamino)benzaldehyde 4-methylthiosemicarbazone (HL3), have been synthesized and characterized. The three palladium(II) complexes 1-3 were prepared respectively from HL1, HL2, and HL3. The crystal structures of two coordination compounds, namely Pd(L2)2 (2) and Pd(L3)2 (3), were obtained, which showed the expected square-planar environment for the metal centers. The ligand HL3 and the Pd(II) complexes 1-3, which are stable in buffered solutions containing up to 5% DMSO, exhibit remarkable inhibitory properties against the aggregation of amyloid-β, reducing the formation of fibrils. HL1, HL3, 2, and 3 display IC50 values (i.e., the concentrations required to reduce Aβ fibrillation by 50%) below 1 μM, lower that of the reference compound catechin (IC50 = 2.8 μM). Finally, in cellulo studies with E. coli cells revealed that the palladium(II) compounds are significantly more efficient than the free ligands in inhibiting Aβ aggregation inside bacterial inclusion bodies, thus illustrating a beneficial effect of metal coordination.

Silver(I) complexes of 3-methoxy-4-hydroxybenzaldehyde thiosemicarbazones and triphenylphosphine: structural, cytotoxicity, and apoptotic studies.

Novel silver(i) complexes of the type [AgCl(PPh3)2(L)] {PPh3 = triphenylphosphine; L = VTSC = 3-methoxy-4-hydroxybenzaldehyde thiosemicarbazone (1); VMTSC = 3-methoxy-4-[2-(morpholine-1-yl)ethoxy]benzaldehyde thiosemicarbazone (2); VPTSC = 3-methoxy-4-[2-(piperidine-1-yl)ethoxy]benzaldehyde thiosemicarbazone (3)} were synthesized and fully characterized by spectroscopic techniques. The molecular structures of complexes 2 and 3 were determined by single crystal X-ray diffraction. Compounds 1-3 exhibited appreciable cytotoxic activity against human tumor cells (lung A549, breast MDA-MB-231 and MCF-7) with IC50 values in 48 h of incubation ranging from 5.6 to 18 μM. Cellular uptake studies showed that complexes 1-3 were efficiently internalized after 3 hours of treatment in MDA-MB-231 cells. The effects of complex 1 on the cell morphology, cell cycle, induction of apoptosis, mitochondrial membrane potential (Δψm), and reactive oxygen species (ROS) production have been evaluated in triple negative breast cancer (TNBC) cells MDA-MB-231. Our results showed that complex 1 induced typical morphological alterations of cell death, an increase in cells at the sub-G1 phase, apoptosis, and mitochondrial membrane depolarization. Furthermore, DNA binding studies evidenced that 1 can bind to ct-DNA and does so without modifying the B-structure of the DNA, but that the binding is weak compared to that of Hoechst 33258.

Solution equilibrium, structural and cytotoxicity studies on Ru(η6-p-cymene) and copper complexes of pyrazolyl thiosemicarbazones

Solution chemical properties of two bidentate pyrazolyl thiosemicarbazones 2-((3-methyl-1-phenyl-1H-pyrazol-4-yl)methylene)hydrazinecarbothioamide (Me-pyrTSC), 2-((1,3-diphenyl-1H-pyrazol-4-yl)methylene)hydrazinecarbothioamide (Ph-pyrTSC), stability of their Cu(II) and Ru(η6-p-cymene) complexes were characterized in aqueous solution (with 30% DMSO) by the combined use of UV–visible spectrophotometry, 1H NMR spectroscopy and electrospray ionization mass spectrometry in addition to their solid phase isolation. The solid phase structures of Me-pyrTSC∙H2O, [Ru(η6-p-cymene)(Me-pyrTSC)Cl]Cl and [Cu(Ph-pyrTSCH−1)2] were determined by single crystal X-ray diffraction. High stability mononuclear Ru(η6-p-cymene) complexes with (N,S) coordination mode are formed in the acidic pH range, and increasing the pH the predominating dinuclear [(Ru(η6-p-cymene))2(L)2]2+ complex with μ2-bridging sulphur donor atoms is formed (where L− is the deprotonated thiosemicarbazone). [CuL]+ and [CuL2] complexes show much higher stability compared to that of complexes of the reference compound benzaldehyde thiosemicarbazone. [CuL2] complexes predominate at neutral pH. Me-pyrTSC and Ph-pyrTSC exhibited moderate cytotoxicity against human colonic adenocarcinoma cell lines (IC50 = 33–76 μM), while their complexation with Ru(η6-p-cymene) (IC50 = 11–24 μM) and especially Cu(II) (IC50 = 3–6 μM) resulted in higher cytotoxicity. Cu(II) complexes of the tested thiosemicarbazones were also cytotoxic in three breast cancer and in a hepatocellular carcinoma cell line. No reactive oxygen species production was detected and the relatively high catalase activity of SUM159 breast cancer cells was decreased upon addition of the ligands and the complexes. In the latter cell line the tested compounds interfered with the glutathione synthesis as they decreased the concentration of this cellular reductant.