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The syntheses of five new complexes of the 2- formylpyridinethiosemicarbazone ligand (HFpyTSC) with Pd(II) and Rh(III) ions are described, viz., [Pd(FpyTSC)(PPh3)]PF6, [Pd(FpyTSC)(SCN)], [Pd(FpyTSC)Br], [Pd(HFpyTSC)2]Brsu

The present study highlights the apoptotic activity of magnetic Fe3O4 nanoparticulates functionalized by glutamic acid and 2-pyridinecarboxaldehyde thiosemicarbazone (PTSC) toward human lung epithelial carcinoma A549 cell line. To this aim, the Fe3O4 nanoparticulates were prepared using co-precipitation method. Then, the glutamic acid and Fe3O4 nanoparticulates were conjugated to each other. The product was further functionalized with bio-reactive PTSC moiety. In addition, the synthesized Fe3O4@Glu/PTSC nanoparticulates were characterized by physico-chemical techniques including scanning electron microscope (SEM), energy dispersive X-ray (EDX), X-ray diffraction (XRD), Fourier-transform infrared (FT–IR) spectroscopy and zeta potential analysis. The effects of in vitro cell viability in Fe3O4@Glu/PTSC nanoparticulate indicated the anti-proliferative properties in a dose-dependent manner (IC50 = 135.6?μM/mL). The high selectivity for tumor cells and far below of activity in HEK293 non-tumorigenic cells is considered as an important feature for this complex (SI, 3.48). Based on the results, PTSC failed to reveal any activity against A549 cells alone. However, Fe3O4 nanoparticulates had some effects in inhibiting the growth of lung cancer cell. Furthermore, Bax and Bcl-2 gene expressions were quantified by real-time PCR method. The expression of Bax increased 1.62-fold, while the expression of Bcl-2 decreased 0.76-fold at 135.6?μM/mL concentration of Fe3O4@Glu/PTSC compared to untreated A549 cells. Furthermore, the Fe3O4@Glu/PTSC nanoparticulate-inducing apoptosis properties were evaluated by Hoechst 33258 staining, Caspase-3 activation assay and Annexin V/propidium iodide staining. The results of the present study suggest that Fe3O4@Glu/PTSC nanoparticulates exhibit effective anti-cancer activity against lung cancer cells.

Ni(II) and Cu(II) complexes having the general composition [M(L)2X2] [where L = 2-pyridinecarboxaldehyde thiosemicarbazone, M = Ni(II) and Cu(II), X = Cl-, NO3- and 1/2 SO42-] have been synthesized. All the metal complexes were characterized by elemental analysis, molar conductance, magnetic moment, mass, IR, EPR and electronic spectral studies. The magnetic moment measurements of the complexes indicate that all the complexes are of high-spin type. On the basis of spectral studies an octahedral geometry has been assigned for Ni(II) complexes whereas tetragonal geometry for Cu(II) except [Cu(L)2SO4] which posseses five coordinated geometry. The ligand and its metal complexes were screened against phytopathogenic fungi and bacteria in vitro.

Four binuclear Cu(II)-Schiff base complexes were synthesized and characterized.Cu complexes have high anticancer activity.Cu complexes induce cells apoptosis possible via intrinsic ROS-mediated mitochondrial pathway.Cu complexes regulate Bcl-2 family prot

A new simple 3-in-1 multi-response thiosemicarbazone-based chemosensor has been synthesized and characterized. The probe not only exhibited high sensitivity towards the most familiar and abundant group 12 metal ions, viz., Zn2+, Cd2+ and Hg2+, in MeCN-H2O (1 : 1, v/v) medium but also can efficiently distinguish them through significant changes in their absorption and emission spectral behavior. The selectivity response was found to follow the order Hg2+, Cd2+, Zn2+ due to the different degrees of stability of their respective complexes, which was further established by TDDFT calculations and interference studies. The binding affinities of the probe towards these metal ions were investigated by absorption, fluorescence emission, fluorescence lifetime, mass spectral and 1H NMR spectral measurements. The effects of solvent polarity on the probe molecule were also examined. Due to the observation of different binding affinities and the ensuing significant changes in absorbance at different wavelengths by a combination of different inputs, L can be judiciously applied for the construction of some basic logic gates (AND, OR, NOT, IMPLICATION and INHIBIT).

To overcome the resistance of cancer cells to platinum-based drugs and effectively suppress tumor growth, we developed a novel indium (In) agent based on liposomes (Lips). Thus, we not only obtained an In(III) thiosemicarbazone agent (5b) with remarkable

In this study, we proposed to design effective multi-target anticancer agents based on the chelation of nontoxic metals with ligands that possess anticancer activity. In total, five Sn(ii) pyridine-2-carboxaldehyde thiosemicarbazone complexes are synthesi

Background: Recently, researchers have been warning about the increased mortality of the various cancer types. Also, the lung adenocarcinoma and the glioma types are burning issues for world's health due to late or wrong diagnosis and/or insufficient treatment methods. For this purpose, our research group designed and synthesized novel 4,5-dimethyl thiazole-hydrazone derivatives which were tested against cancer and normal cell lines to understand the structure-activity relationship (SAR). Methods: The lead compounds were obtained by reacting 2-(substituted aryl-2-ylmethylene) hydrazin-1-carbothioamide with 3-chloro-2-butanone derivatives. The structural elucidation of the compounds was performed by1H-NMR,13C-NMR, and LC/MS-IT-TOF spectral and elemental analyses. The synthesized compounds were tested in vitro for the anticancer activity against A549 human lung adenocarcinoma and C6 rat glioma cells and investigated for which pathway to induce cell death. Also, the docking study of the active compounds was achieved to understand the SAR. Results: The targeted compounds (2a-2l) were synthesized successfully above 70% yields, and the analysis findings proved their purity. In general, the results of activity studies displayed significant effects against at least one cell line, except compounds 2e (indol-3-yl) and 2h (4-dimethylaminophenyl). Furthermore, compounds 2b and 2f displayed potential anticancer activity. With the help of molecular docking study, a potential selectivity of compound 2f was observed for type II protein kinase. On the other hand, compound 2b interacted with the active site nearly the same as Dasatinib. Therefore, these two compounds could be used as a base on developing selective anticancer drugs. Conclusion: Pyridin-2-yl (2b) derivative was found to be a favorable molecule with high anticancer potency against C6 and A549 cell lines. Additionally, 1-naphthyl (2f) derivative was a worthy compound for potential selectivity. In future studies, it will be our priority to focus on developing derivatives of these two compounds (2b and 2f) and elucidate their mechanisms.

The superbug infection caused by metallo-β-lactamases (MβLs) carrying drug-resistant bacteria, specifically, New Delhi metallo-β-lactamase (NDM-1) has become an emerging threat. In an effort to develop novel inhibitors of NDM-1, thirteen thiosemicarbazones (1a-1m) were synthesized and assayed. The obtained molecules specifically inhibited NDM-1, with an IC50 in the range of 0.88–20.2 μM, and 1a and 1f were found to be the potent inhibitors (IC50 = 1.79 and 0.88 μM) using cefazolin as substrate. ITC and kinetic assays indicated that 1a irreversibly and non-competitively inhibited NDM-1 in vitro. Importantly, MIC assays revealed that these molecules by themselves can sterilize NDM-producing clinical isolates EC01 and EC08, exhibited 78-312-fold stronger activities than the cefazolin. MIC assays suggest that 1a (16 μg ml?1) has synergistic antimicrobial effect with ampicillin, cefazolin and meropenem on E. coli producing NDM-1, resulting in MICs of 4-32-, 4-32-, and 4-8-fold decrease, respectively. These studies indicate that the thiosemicarbazide is a valuable scaffold for the development of inhibitors of NDM-1 and NDM-1 carrying drug-resistant bacteria.

The invention discloses an FTO small molecule inhibitor palladium complex and a synthesis method thereof. The synthesis method comprises the following steps: dissolving thiosemicarbazide in anhydrousCH3OH, then adding 2-pyridylaldehyde, carrying out reflu

The invention discloses a tin complex taking 2-pyridineformaldehyde thiosemicarbazone as a ligand and a synthesis method thereof. The synthesis method comprises the following steps of: dissolving thiosemicarbazone in anhydrous CH3OH, adding 2-pyridineform

Objectives: In the prospection of possible agents against neglected diseases, thiazole compounds are presented as promising candidates and are known to have activity against trypanosomatid parasites. Thus, this work aimed to evaluate the effects of thiazo

The invention discloses an indium compound taking 2-pyridylaldehyde thiosemicarbazone as a ligand as well as a synthesis method and application thereof. The synthesis method comprises the following steps: dissolving thiosemicarbazide into methanol; after

The invention discloses a platinum complex taking 2-pyridine formaldehyde thiosemicarbazone as ligand and a synthesis method and application thereof. The synthesis method includes: dissolving thiosemicarbazone in methanol, adding 2-pyridylaldehyde after d

Taking into consideration the eminence of 1,3-thiazoles in medicinal chemistry and in a view of procuring more pronounced biological contour, the synthesis of 2-(2-arylidenehydrazinyl)-4-arylthiazoles 6–43 was made possible by the cyclization reaction of thiosemicarbazones and α-bromoacetophenones. The thiosemicarbazones 5a-m were in turn synthesized from substituted benzaldehydes or acetophenones and thiosemicarbazide. Optimization of the reaction conditions was carried out in order to attain the target molecules in good yields. All the new compounds were evaluated in vitro for their antiviral activity against the replication of HIV-1 and HIV-2 in MT4 cells using a MTT assay. Screening results indicated that compounds 32–34 are the only compounds in the series inhibiting HIV-1 and HIV-2 replication in cell cultures with IC50 of >2.71, >2.19 and > 1.71 μM, respectively. The molecular docking of compounds 32 and 34 with some amino acids of human immunodeficiency virus reverse transcriptase (HIV RT) were also studied. The preliminary quantum structure-activity relationship (QSAR) among the newly synthesized congeners was obtained by two methods, Multiple Linear Regression (MRL) and Genetic Function Approximation (GFA).

Provided herein are compounds useful as inhibitors of CBX. Also described are pharmaceutical compositions and medical uses of these compounds.

Synthesis and X-ray structural characterization of pyridine-2- carboxaldehyde thiosemicarbazone (L), and its metal complexes, [Cu(L)(OH2)](ClO4)2 and [Pb(L)(ONO2)2]n are reported. X-ray diffraction reveals that the metal centres in the two complexes are distorted square planar and square pyramid geometries, respectively. Among the three compounds [Cu(L)(OH2)](ClO4)2 is found to be active against human keratinocyte cell line.

In the search for compounds which may inhibit the development of melanomas, a series of thiosemicarbazones has been investigated as possible inhibitors of the tyrosinase enzyme. The results showed that all the thiosemicarbazones tested exhibited significant inhibitory effects on the enzyme. Thiosemicarbazones Thio-1, Thio-2, Thio-3 and Thio-4 substituted with oxygenate moieties, were better inhibitors (IC50 0.42, 0.35, 0.36 and 0.44?mM, respectively) than Thio-5, Thio-6, Thio-7 and Thio-8. For the better inhibitors, molecular docking results suggested that the oxygen present in the para position of the aromatic ring is essential for the tyrosinase inhibition, due its high ability for complexation with Cu2+ ions. Inside the active protein pocket, Thio-2 – the best studied inhibitor – is able to interact with the amino acid residues His-155, Gly-170 and Val-172 via hydrogen bonding and hydrophobic force. Thio-2, containing a substituent on the aromatic ring similar to the substrate L-DOPA, showed a competitive inhibition mechanism as viewed in a Lineweaver–Burk plot. The same results were observed in the UV–Vis curves.

With reference to recent studies reporting on the various biological properties of the thiazolidinone scaffold, we synthesized more than a hundred compounds characterized by a 1,3-thiazolidin-4-one nucleus derivatised at the C2 with a hydrazine bridge linked to (cyclo)aliphatic or hetero(aryl) moieties, and their N-benzylated derivatives. These molecules were assayed as potential anti-Candida agents and they were shown to possess comparable, and in some cases higher biological activity than well-established topical and systemic antimycotic drugs (i.e. clotrimazole, fluconazole, ketoconazole, miconazole, tioconazole, amphotericin B). Compounds endowed with the lowest MICs underwent further testing in order to assess their cytotoxic effect (CC50) on Hep2 cells, which demonstrated their relative safety. Finally, QSAR and 3-D QSAR models were used to predict putative chemical modifications of the 1,3-thiazolidin-4-one scaffold in order to design new and potential more active compounds against Candida spp.

A small series of 2-(hetero(aryl)methylene) hydrazine-1-carbothioamides including two aryl derivatives was synthesized and tested for their inhibitory activity against urease. Compound (E)-2-(Furan-2-ylmethylene) hydrazine-1-carbothioamide (3f), having a furan ring, was the most potent inhibitor of urease with an IC50 value of 0.58 μm. Molecular modeling was carried out through docking the designed compounds into the urease binding site to predict whether these derivatives have analogous binding mode to the urease inhibitors. The study revealed that all of the tested compounds bind with both metal atoms at the active site of the enzyme. The aromatic ring of the compounds forms ionic interactions with the residues, Ala(440), Asp(494), Ala(636), and Met(637).

A facile synthesis of bis-thiazoles, bis-pyrazoles, and bis-hydrazonates from the reaction of bis-hydrazonoyl dichlorides with different moieties is described. Bis-triazolothiadiazoles were synthesized via oxidative cyclization of bis-hydrazones. Structures of the final product were elucidated by elemental analyses and spectral data.

Antimitotic agents are widely used in cancer chemotherapy but the numerous side effects and the onset of resistance limit their clinical efficacy. Therefore, with the purpose of discovering more selective and efficient anticancer agents to be administered alone or in combination with traditional drugs, we synthesized a large library of 1,3,4-thiadiazoline analogues, maintaining the pharmacophoric structure of an antiproliferative compound known as K858: this is a new inhibitor of kinesin Eg5, able to induce the mitotic arrest in colorectal cancer cells and in xenograft ovarian cancer cells. We screened 103 compounds to assess their antiproliferative activity on PC3 prostate cancer cell line. Two derivatives, compounds 32 (corresponding to K858) and 33, have shown to be the most effective against prostate tumor cells and also towards two melanoma cell lines (SK-MEL-5 and SK-MEL-28) at low micromolar concentrations, confirming the pharmacological activity of this scaffold and revealing the potential role of 1,3,4-thiadiazolines in the management of cancer.

The search for newer histone deacetylase (HDAC) inhibitors has attracted a great deal of interest of medicinal chemists worldwide, especially after the first HDAC inhibitor (Zolinza , widely known as SAHA or Suberoylanilide hydroxamic acid) was approved by the FDA for the treatment of Tcell lymphoma in 2006. As a continuity of our ongoing research in this area, we designed and synthesized a series of 5-aryl-1,3,4-thiadiazole-based hydroxamic acids as analogues of SAHA and evaluated their biological activities. Most of the compounds in this series, e.g. compounds with 5-aryl moiety being 2-furfuryl (5a), 5-bromofuran-2-yl (5b), 5-methylfuran-2-yl (5c), thiophen-2-yl (5d), 5-methylthiophen-2-yl (5f) and pyridyl (5g-i), were found to have potent anticancer cytotoxicity with IC50 values of generally 5-to 10-fold lower than that of SAHA in 4 human cancer cell lines assayed. Those compounds with potent cytotoxicity were also found to have strong HDAC inhibition effects. Docking studies revealed that compounds 5a and 5d displayed high affinities towards HDAC2 and 8.

Two new complexes, [Ni(HL1)(N3)(μ 1,1N3)]2 (1) [HL1: NC 5H4CH3C=NNH (C=O) NH2] and [Ni(L2)N3] (2) [HL2: NC5H 4HC=N NH(C=S)NH2], have been synthesized by reaction of Ni(OAC)2·4H2O and sodium azide with HL1 and HL2 and characterized by elemental analysis, FT-IR, and UV-vis spectral studies. Single-crystal X-ray diffraction reveals that 1 is dinuclear with nickel(II) in an octahedral environment of NNO donors of HL1, two nitrogens of azide bridges and one nitrogen of terminal azide; 2 is mononuclear containing nickel(II) in a distorted square-planar environment of NNS donors of HL2 and one terminal azide. The structures of 1 and 2 have been optimized by density functional theory. The results of antimicrobial activities of ligands, 1 and 2 demonstrated that HL2 and 2 have good antimicrobial activity in contrast with HL1 and 1, related to the presence of sulfur donor in HL2. 2014

Melanin play a major role in human skin protection and their biosynthesis is vital. Due to their color, they contribute to the skin pigmentation. Tyrosinase is a key enzyme involved in the first stage of melanin biosynthesis, it catalyzes the transformation of tyrosine into l-dopaquinone. The aim of the present study was to study molecules able to inhibit tyrosinase to be used in treating depigmentation-related disorders. In this study, we targeted arylthiosemicarbazone analogs with the aim to contribute to the identification of the optimal aryl ring to be linked to the thiosemicarbazone moiety. The biological activity was evaluated on commercial mushroom tyrosinase which was purified prior use. The results demonstrated that several of our compounds (1a-h, 1j, 1r and 5) had more potent inhibitory activities than kojic acid which was used as the reference inhibitor.

The first metal complexes of 3-aminopyridine-2-carboxaldehyde thiosemicarbazone (Triapine) were synthesized. Triapine was prepared by a novel three-step procedure in 64% overall yield. In addition, a series of related ligands, namely, 2-formylpyridine thiosemicarbazone, 2-acetylpyridine thiosemicarbazone, 2-pyridineformamide thiosemicarbazone, and their N 4-dimethylated derivatives (including the N4-dimethylated analogue of Triapine) were prepared, along with their corresponding gallium(III) and iron(III) complexes with the general formula [M(L)2] +, where HL is the respective thiosemicarbazone. The compounds were characterized by elemental analysis, 1H and 13C NMR, IR and UV-vis spectroscopies, mass spectrometry, and cyclic voltammetry. In addition, Triapine and its iron(III) and gallium(III) complexes were studied by X-ray crystallography. All ligands and complexes were tested for their in vitro antiproliferative activity in two human cancer cell lines (41M and SK-BR-3), and structure-activity relationships were established. In general, the coordination to gallium(III) increased the cytotoxicity while the iron(III) complexes show reduced cytotoxic activity compared to the metal-free thiosemicarbazones. Selected compounds were investigated for the capacity of inhibiting ribonucleotide reductase by incorporation of 3H-cytidine into DNA.

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