1200-00-6Relevant academic research and scientific papers
Structural and spectral studies of thiosemicarbazones derived from 3- and 4-formylpyridine and 3- and 4-acetylpyridine
Mendes,Teixeira,Lima,Beraldo,Speziali,West
, p. 355 - 360 (2001)
Crystal structures of thiosemicarbazones prepared from 3- and 4-formylpyridine and 3- and 4-acetylpyridine are included along with their UV spectra. 4-Formylpyridine thiosemicarbazone has the following structural properties: monoclinic, P21÷n, a = 7.2420(5), b = 13.961(1), c = 8.415(1) A?, β = 90.90(1)°, V = 850.7(1) A?3 and Z = 4; for 3-formylpyridine thiosemicarbazone: monoclinic, C2÷c, a = 13.661(2), b = 7.1120(4), c = 19.046(2) A?, β = 107.71(1)°, V = 1762.8(3) A?3 and Z = 8; for 4-acetylpyridine thiosemicarbazone: triclinic, P-1, a = 8.104(3), b = 8.512(2), c = 8.708(3) A?, α = 83.85(0), β = 66.66(0), γ = 62.87(0)°, V = 488.9(3) A?3 and Z = 2; for 3-acetylpyridine thiosemicarbazone monoclinic, P21÷a, a = 8.408(1), b = 11.853(2), = c = 9.777(3) A?, β = 97.66(2)°, V = 985.7(4) A?3 and Z = 4. Intramolecular and intermolecular hydrogen bonding are both present. There is a difference in the angles between the mean planes of the pyridine ring and thiosemicarbazone moiety in the two series.
Synthesis and selective human monoamine oxidase b inhibition of heterocyclic hybrids based on hydrazine and thiazole scaffolds
Carradori, Simone,D'Ascenzio, Melissa,De Monte, Celeste,Secci, Daniela,Yá?ez, Matilde
, p. 17 - 22 (2013)
A new scaffold of hydrazothiazoles has been designed as monoamine oxidase (MAO) inhibitors combining the hydrazine moiety of iproniazid and the thiazole nucleus of glitazones, a class of peroxisome proliferator-activated receptor (PPAR)γ agonists recently co-crystallized with human MAO-B. The resulting derivatives were synthesized and assayed to evaluate their in vitro activity against both the A and B isoforms of hMAO. All compounds were shown to be selective hMAO-B inhibitors with IC50 values in the low micromolar/high nanomolar range. Such results suggest that the hydrazothiazole scaffold could be considered as an interesting pharmacophore for the future design of new lead compounds as coadjuvants for the treatment of neurodegenerative diseases. The hydrazothiazole scaffold has been designed combining the hydrazide moiety of iproniazid and the thiazole nucleus of glitazones, a class of peroxisome proliferator-activated receptor γ agonists recently co-crystallized with human monoamine oxidase B (hMAO-B). The resulting derivatives were assayed to evaluate their in vitro inhibitory activity against both the A and B isoforms of hMAO. All compounds were shown to be selective and potent hMAO-B inhibitors in the low micromolar/high nanomolar range. Copyright
Computational studies of 4-formylpyridinethiosemicarbazone and structural and biological studies of its Ni(II) and Cu(II) complexes
Sripathi, Mydhili P.,Berely, Sireesha,Ramana Reddy, Chittireddy Venkata
, (2019)
To understand the stability, chelation behaviour, and biological activity of 4-Formylpyridinethiosemicarbazone (H4FPT), it is important to recognize its interactive geometry. Hence, computational studies on geometrically optimized structures of thione and thiol forms of H4FPT were performed. Binary metal complexes of the ligand, H4FPT (L) with the Ni(II) and Cu(II) metal ions (M), were synthesized and characterized by various spectroanalytical techniques as elemental analysis, molar conductance, magnetic susceptibility measurements, LC-MS, TGA, IR, UV-Visible, ESR, and powder XRD. Elemental analysis, LC-MS, and TGA studies indicate 1:2 (ML2) composition for mononuclear Ni(II) complex and 1:1 (ML) composition for dinuclear Cu(II) complex. Electronic absorption titrations, fluorescence quenching studies, and viscosity measurements suggest intercalative mode of binding of the complexes with calf thymus DNA (CT-DNA). These complexes also promote hydrolytic cleavage of plasmid pBR322. The ligand (H4FPT) and its complexes showed moderate-to-good activity against Gram-positive and Gram-negative bacterial strains. The DPPH radical scavenging studies showed antioxidant nature of both complexes.
Synthesis, characterization and biological activities of semicarbazones and their copper complexes
Venkatachalam, Taracad K.,Bernhardt, Paul V.,Noble, Chris J.,Fletcher, Nicholas,Pierens, Gregory K.,Thurecht, Kris J.,Reutens, David C.
, p. 295 - 308 (2016)
Substituted semicarbazones/thiosemicarbazones and their copper complexes have been prepared and several single crystal structures examined. The copper complexes of these semicarbazone/thiosemicarbazones were prepared and several crystal structures examined. The single crystal X-ray structure of the pyridyl-substituted semicarbazone showed two types of copper complexes, a monomer and a dimer. We also found that the p-nitrophenyl semicarbazone formed a conventional ‘magic lantern’ acetate-bridged dimer. Electron Paramagnetic Resonance (EPR) of several of the copper complexes was consistent with the results of single crystal X-ray crystallography. The EPR spectra of the p-nitrophenyl semicarbazone copper complex in dimethylsulfoxide (DMSO) showed the presence of two species, confirming the structural information. Since thiosemicarbazones and semicarbazones have been reported to exhibit anticancer activity, we examined the anticancer activity of several of the derivatives reported in the present study and interestingly only the thiosemicarbazone showed activity while the semicarbazones were not active indicating that introduction of sulphur atom alters the biological profile of these thiosemicarbazones.
Recent advances in the development of selective human MAO-B inhibitors: (Hetero)arylidene-(4-substituted-thiazol-2-yl)hydrazines
Secci, Daniela,Bolasco, Adriana,Carradori, Simone,D'Ascenzio, Melissa,Nescatelli, Riccardo,Yá?ez, Matilde
, p. 405 - 417 (2012)
A large series of (4-substituted-thiazol-2-yl)hydrazine derivatives was synthesized in good yield and assayed for their in vitro human monoamine oxidase (hMAO) inhibitory activity and selectivity. Most of them showed inhibitory activity in the nanomolar range and hMAO-B selective inhibition higher than reference drugs, demonstrating our interest in this privileged scaffold. The structure-activity relationship of the different rings on the N1-hydrazine position indicated that a pyridine ring was preferred with the presence of electron-withdrawing substituents on the aryl group at C4 of the thiazole nucleus. The substituent on the α-carbon to the N1-hydrazine moiety (methyl or hydrogen) had a great influence on the activity and hMAO-B selectivity. Moreover, the reversibility of the enzyme inhibition for the best active compound was reported.
2-(hetero(aryl)methylene)hydrazine-1-carbothioamides as potent urease inhibitors
Saeed, Aamer,Imran, Aqeel,Channar, Pervaiz A.,Shahid, Mohammad,Mahmood, Wajahat,Iqbal, Jamshed
, p. 225 - 230 (2015)
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).
Thiosemicarbazones exhibit inhibitory efficacy against New Delhi metallo-β-lactamase-1 (NDM-1)
Ge, Ying,Kang, Peng-Wei,Li, Jia-Qi,Gao, Han,Zhai, Le,Sun, Le-Yun,Chen, Cheng,Yang, Ke-Wu
, p. 574 - 579 (2021)
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.
Sonochemical synthesis of the novel 1D zig-zag Hg(II)-Iodo bridged metal-organic coordination compounds with thiosemicarbazide derivative ligand
Hanifehpour, Younes,Dadashi, Jaber,Khaleghian, Mohammad,Rezaei, Mahboube,Mirtamizdoust, Babak,Joo, Sang Woo
, (2021/11/27)
In the present research, a novel mercury (II) metal organic coordination compound, [Hg(Q)I2]n (Q = pyridine-4-carbaldehyde thiosemicarbazide) with nano rods shape was prepared applying an ultrasonic manner. The synthesized compound was determined with infrared spectroscopy (IR), scanning electron microscopy (SEM), and X-ray diffraction (XRD). In solid-state, the coordination polymer takes the appearance of a zig-zag 1D polymer. The coordination number of Hg (II) is four by one sulfur atom of organic ligand and three iodine atoms which two of iodine atoms are coordinated to other repeating units, and one of iodine is unattached. The zig-zag 1D chains interact with neighboring chains via weak interactions, making a 3D supramolecular metal organic polymer. It was found that using high-intensity ultrasound is a facile, versatile, and eco-friendly synthetic instrument for supramolecular coordination compounds. Also, types of non-covalent interactions in the structure cause extraordinary flexibility to perform secondary interactions and create the property of attracting guests to this host.
Design and efficient synthesis of novel 4,5-dimethylthiazole-hydrazone derivatives and their anticancer activity
Evren, Asaf Evrim,Yurtta?, Leyla,Ekselli, Bü?ra,Aksoy, Onur,Akalin-?ift?i, Gül?en
, p. 372 - 386 (2021/06/17)
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.
Design, synthesis, biological evaluation, QSAR analysis and molecular modelling of new thiazol-benzimidazoles as EGFR inhibitors
Abd El-Karim, Somaia S.,Ahmed, Nesreen S.,Anwar, Manal M.,El-Hallouty, Salwa M.,Srour, Aladdin M.
supporting information, (2020/08/06)
Heterocyclic rings such as thiazole and benzimidazole are considered as privileged structures, since they constitute several FDA-approved drugs for cancer treatment. In this work, a new set of 2-(2-(substituted) hydrazinyl)-4-(1-methyl-1H-benzo[d]imidazol-2-yl) thiazoles 4a-q were designed as epidermal growth factor receptor (EGFR) inhibitors and synthesized using concise synthetic methods. The new target compounds have been evaluated in vitro for their suppression activity against EGFR TK. Compounds 4n, 4h, 4i, 4a and 4d exhibited significant potency in comparison with erlotinib which served as a reference drug (IC50, 71.67–152.59 nM; IC50 erlotinib, 152.59 nM). Furthermore, MTT assay revealed that compounds 4j, 4a, 4f, 4h, 4n produced the most promising cytotoxic potency against the human breast cancer cell line (MCF-7) (IC50; 5.96–11.91 μM; IC50 erlotinib; 4.15 μM). Compound 4a showed promising activity as EGFR TK inhibitor as well as anti-breast cancer agent. In addition, 4a induced apoptotic effect and cell cycle arrest at G2/M phase preventing the mitotic cycle in MCF-7 cells. Moreover, 4a upregulated the oncogenic parameters; caspase-3, p53, Bax/Bcl-2 as well as it inhibited the level of PARP-1 enzyme. QSAR study was carried out for the new derivatives and it revealed the goodness of the models. Furthermore, molecular docking studies represented the binding modes of the promising compounds in the active pocket of EGFR.
