- Structural and spectral studies of thiosemicarbazones derived from 3- and 4-formylpyridine and 3- and 4-acetylpyridine
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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.
- Mendes,Teixeira,Lima,Beraldo,Speziali,West
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- Synthesis and selective human monoamine oxidase b inhibition of heterocyclic hybrids based on hydrazine and thiazole scaffolds
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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
- Carradori, Simone,D'Ascenzio, Melissa,De Monte, Celeste,Secci, Daniela,Yá?ez, Matilde
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- Computational studies of 4-formylpyridinethiosemicarbazone and structural and biological studies of its Ni(II) and Cu(II) complexes
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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.
- Sripathi, Mydhili P.,Berely, Sireesha,Ramana Reddy, Chittireddy Venkata
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- Synthesis, characterization and biological activities of semicarbazones and their copper complexes
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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.
- Venkatachalam, Taracad K.,Bernhardt, Paul V.,Noble, Chris J.,Fletcher, Nicholas,Pierens, Gregory K.,Thurecht, Kris J.,Reutens, David C.
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- Recent advances in the development of selective human MAO-B inhibitors: (Hetero)arylidene-(4-substituted-thiazol-2-yl)hydrazines
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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.
- Secci, Daniela,Bolasco, Adriana,Carradori, Simone,D'Ascenzio, Melissa,Nescatelli, Riccardo,Yá?ez, Matilde
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- 2-(hetero(aryl)methylene)hydrazine-1-carbothioamides as potent urease inhibitors
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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).
- Saeed, Aamer,Imran, Aqeel,Channar, Pervaiz A.,Shahid, Mohammad,Mahmood, Wajahat,Iqbal, Jamshed
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- Thiosemicarbazones exhibit inhibitory efficacy against New Delhi metallo-β-lactamase-1 (NDM-1)
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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.
- Ge, Ying,Kang, Peng-Wei,Li, Jia-Qi,Gao, Han,Zhai, Le,Sun, Le-Yun,Chen, Cheng,Yang, Ke-Wu
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- Sonochemical synthesis of the novel 1D zig-zag Hg(II)-Iodo bridged metal-organic coordination compounds with thiosemicarbazide derivative ligand
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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.
- Hanifehpour, Younes,Dadashi, Jaber,Khaleghian, Mohammad,Rezaei, Mahboube,Mirtamizdoust, Babak,Joo, Sang Woo
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- Design and efficient synthesis of novel 4,5-dimethylthiazole-hydrazone derivatives and their anticancer activity
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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.
- Evren, Asaf Evrim,Yurtta?, Leyla,Ekselli, Bü?ra,Aksoy, Onur,Akalin-?ift?i, Gül?en
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p. 372 - 386
(2021/06/17)
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- Design, synthesis, biological evaluation, QSAR analysis and molecular modelling of new thiazol-benzimidazoles as EGFR inhibitors
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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.
- Abd El-Karim, Somaia S.,Ahmed, Nesreen S.,Anwar, Manal M.,El-Hallouty, Salwa M.,Srour, Aladdin M.
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supporting information
(2020/08/06)
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- Regioselective N(2)-H-functionalization of thiosemicarbazones of aromatic and heteroaromatic aldehydes with acrylonitrile
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Regioselective N(2)-H-cyanoethylation of thiosemicarbazones of aromatic and heteroaromatic aldehydes with acrylonitrile proceeds under mild conditions (14% KOH, acetone/H2O, 35 °C, 6–21 h) to afford 1-(2-сyanoethyl)-2-[(E)-aryl(heteroaryl)methylidene]-1-hydrazinecarbothioamides in up to 74% yields. The synthesized thioamides are promising precursors of novel families of functionalized thiosemicarbazones as exemplified by hydrolysis of their cyano group to the corresponding amido function (46.5–60% yields).
- Mal’kina, Anastasiya G.,Nosyreva, Valentina V.,Albanov, Alexander I.,Afonin, Andrei V.,Vashchenko, Alexander V.,Amosova, Svetlana V.,Trofimov, Boris A.
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supporting information
p. 159 - 168
(2017/01/10)
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- Synthesis, biological evaluation and quantitative structure-active relationships of 1,3-thiazolidin-4-one derivatives. A promising chemical scaffold endowed with high antifungal potency and low cytotoxicity
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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.
- Carradori, Simone,Bizzarri, Bruna,D'Ascenzio, Melissa,De Monte, Celeste,Grande, Rossella,Rivanera, Daniela,Zicari, Alessanda,Mari, Emanuela,Sabatino, Manuela,Patsilinakos, Alexandros,Ragno, Rino,Secci, Daniela
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p. 274 - 292
(2017/10/05)
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- Synthesis of a sugar-based thiosemicarbazone series and structure-activity relationship versus the parasite cysteine proteases rhodesain, cruzain, and Schistosoma mansoni cathepsin B1
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The pressing need for better drugs against Chagas disease, African sleeping sickness, and schistosomiasis motivates the search for inhibitors of cruzain, rhodesain, and Schistosoma mansoni CB1 (SmCB1), the major cysteine proteases from Trypanosoma cruzi, Trypanosoma brucei, and S. mansoni, respectively. Thiosemicarbazones and heterocyclic analogues have been shown to be both antitrypanocidal and inhibitory against parasite cysteine proteases. A series of compounds was synthesized and evaluated against cruzain, rhodesain, and SmCB1 through biochemical assays to determine their potency and structure-activity relationships (SAR). This approach led to the discovery of 6 rhodesain, 4 cruzain, and 5 SmCB1 inhibitors with 50% inhibitory concentrations (IC50s) of ≤10 μM. Among the compounds tested, the thiosemicarbazone derivative of peracetylated galactoside (compound 4i) was discovered to be a potent rhodesain inhibitor (IC50 = 1.2 ± 1.0 μM). The impact of a range of modifications was determined; removal of thiosemicarbazone or its replacement by semicarbazone resulted in virtually inactive compounds, and modifications in the sugar also diminished potency. Compounds were also evaluated in vitro against the parasites T. cruzi, T. brucei, and S. mansoni, revealing active compounds among this series.
- Fonseca, Nayara Cristina,Da Cruz, Luana Faria,Da Silva Villela, Filipe,Do Nascimento Pereira, Glaécia Aparecida,De Siqueira-Neto, Jair Lage,Kellar, Danielle,Suzuki, Brian M.,Ray, Debalina,De Souza, Thiago Belarmino,Alves, Ricardo José,Júnior, Policarpo Ademar Sales,Romanha, Alvaro José,Murta, Silvane Maria Fonseca,McKerrow, James H.,Caffrey, Conor R.,De Oliveira, Renata Barbosa,Ferreira, Rafaela Salgado
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p. 2666 - 2677
(2015/06/23)
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- Thiazole compounds with activity against Cryptococcus gattii and Cryptococcus neoformans in vitro
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Human cryptococcosis can occur as a primary or opportunistic infection and develop as an acute, subacute, or chronic, systemic infection involving different host organs. We evaluated the antifungal activity of thirteen compounds against Cryptococcus gattii and Cryptococcus neoformans in vitro, by assessing the toxicity of the compounds showing the greatest antifungal activity in VERO cells and murine macrophages. From these results, four compounds were considered promising for further studies because they displayed low cytotoxicity and significant antifungal activity. The heterocyclic compounds 1b, 1c, 1d, and 1m have antifungal activity levels between that of amphotericin B and fluconazole in vitro. The death curve of Cryptococcus spp. treated with these four compounds was similar to the curve obtained for amphotericin B, in that we observed a significant reduction in cell viability within the first 24 h of treatment. Additionally, we found that there was no effect when these compounds were combined with amphotericin and fluconazole, except for 1c, which antagonized the effect of amphotericin B against C. gattii, also reflected in the reduction of the post-antifungal effect (PAFE); however, this interaction did not alter the ergosterol content. The results shown in this paper reveal the discovery of novel thiazole compounds, which are easy to synthesize, and with potentially exhibit antifungal activity, and display low cytotoxicity in normal mammalian cells. These compounds can be used as prototypes for the design of new antifungal drugs against C. gattii and C. neoformans.
- Pereira de Sá, Nívea,Lino, Cleudiomar Inácio,Fonseca, Nayara Cristina,Borelli, Beatriz Martins,Ramos, Jonas Pereira,Souza-Fagundes, Elaine Maria,Rosa, Carlos Augusto,Santos, Daniel Assis,Barbosa De Oliveira, Renata,Johann, Susana
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p. 233 - 242
(2015/08/24)
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- Synthesis and pharmacological screening of a large library of 1,3,4-thiadiazolines as innovative therapeutic tools for the treatment of prostate cancer and melanoma
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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.
- De Monte, Celeste,Carradori, Simone,Secci, Daniela,D'Ascenzio, Melissa,Guglielmi, Paolo,Mollica, Adriano,Morrone, Stefania,Scarpa, Susanna,Aglianò, Anna Maria,Giantulli, Sabrina,Silvestri, Ida
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p. 245 - 262
(2015/11/03)
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- 5-aryl-1,3,4-thiadiazole-based hydroxamic acids as histone deacetylase inhibitors and antitumor agents: Synthesis, bioevaluation and docking study
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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.
- Huong, Tran Thi Lan,Dung, Do Thi Mai,Oanh, Dao Thi Kim,Lan, Tran Thi Bich,Dung, Phan Thi Phuong,Loi, Vu Duc,Kim, Kyung Rok,Han, Byung Woo,Yun, Jieun,Kang, Jong Soon,Kim, Youngsoo,Han, Sang-Bae,Nam, Nguyen-Hai
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p. 296 - 304
(2016/03/22)
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- Synthesis of a novel series of thiazole-based histone acetyltransferase inhibitors
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Acetylation, which targets a broad range of histone and non-histone proteins, is a reversible mechanism and plays a critical role in eukaryotic genes activation/deactivation. Acetyltransferases are very well conserved through evolution. This allows the use of a simple model organism, such as budding yeast, for the study of their related processes and to discover specific inhibitors. Following a simple yeast-based chemogenetic approach, we have identified a novel HAT (histone acetyltransferase) inhibitor active both in vitro and in vivo. This new synthetic compound, 1-(4-(4-chlorophenyl)thiazol-2- yl)-2-(propan-2-ylidene)hydrazine, named BF1, showed substrate selectivity for histone H3 acetylation and inhibitory activity in vitro on recombinant HAT Gcn5 and p300. Finally, we tested BF1 on human cells, HeLa as control and two aggressive cancer cell lines: a neuroblastoma from neuronal tissue and glioblastoma from brain tumour. Both global acetylation of histone H3 and specific acetylation at lysine 18 (H3AcK18) were lowered by BF1 treatment. Collectively, our results show the efficacy of this novel HAT inhibitor and propose the utilization of BF1 as a new, promising tool for future pharmacological studies.
- Secci, Daniela,Carradori, Simone,Bizzarri, Bruna,Bolasco, Adriana,Ballario, Paola,Patramani, Zoi,Fragapane, Paola,Vernarecci, Stefano,Canzonetta, Claudia,Filetici, Patrizia
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p. 1680 - 1689
(2014/03/21)
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- Evaluation of a large library of (thiazol-2-yl)hydrazones and analogues as histone acetyltransferase inhibitors: Enzyme and cellular studies
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Recently we described some (thiazol-2-yl)hydrazones as antiprotozoal, antifungal and anti-MAO agents as well as Gcn5 HAT inhibitors. Among these last compounds, CPTH2 and CPTH6 showed HAT inhibition in cells and broad anticancer properties. With the aim to identify HAT inhibitors more potent than the two prototypes, we synthesized several new (thiazol-2-yl)hydrazones including some related thiazolidines and pyrimidin-4(3H)-ones, and we tested the whole library existing in our lab against human p300 and PCAF HAT enzymes. Some compounds (1x, 1c', 1d', 1i' and 2m) were more efficient than CPTH2 and CPTH6 in inhibiting the p300 HAT enzyme. When tested in human leukemia U937 and colon carcinoma HCT116 cells (100 μM, 30 h), 1x, 1i' and 2m gave higher (U937 cells) or similar (HCT116 cells) apoptosis than CPTH6, and were more potent than CPTH6 in inducing cytodifferentiation (U937 cells).
- Carradori, Simone,Rotili, Dante,De Monte, Celeste,Lenoci, Alessia,D'Ascenzio, Melissa,Rodriguez, Veronica,Filetici, Patrizia,Miceli, Marco,Nebbioso, Angela,Altucci, Lucia,Secci, Daniela,Mai, Antonello
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p. 569 - 578
(2014/06/09)
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- Design, synthesis and biological characterization of thiazolidin-4-one derivatives as promising inhibitors of Toxoplasma gondii
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We designed and synthesized a large number of novel thiazolidin-4-one derivatives for the evaluation of their anti-Toxoplasma gondii activity. This scaffold was functionalized at the N1-hydrazine portion with aliphatic, cycloaliphatic and (hetero)aromatic moieties. Then, a benzyl pendant was introduced at the lactamic NH of the core nucleus to evaluate the influence of this chemical modification on biological activity. The compounds were subjected to several in vitro assays to assess their anti-parasitic efficacy, cytotoxicity on fibroblasts, inhibition of tachyzoite invasion/attachment and replication after treatment. Results showed that fourteen of these thiazole-based compounds compare favorably to control compound trimethoprim in terms of parasite growth inhibition.
- D'Ascenzio, Melissa,Bizzarri, Bruna,De Monte, Celeste,Carradori, Simone,Bolasco, Adriana,Secci, Daniela,Rivanera, Daniela,Faulhaber, Nathan,Bordón, Claudia,Jones-Brando, Lorraine
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- Synthesis, anti-Candida activity, and cytotoxicity of new (4-(4-iodophenyl)thiazol-2-yl)hydrazine derivatives
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Novel (4-(4-iodophenyl)-thiazol-2-yl)hydrazine derivatives were assayed for their in vitro anti-Candida activity, compared to topical and systemic antifungal drugs, against twenty-seven clinical isolates. The presence of aliphatic chains or specific heteroaromatic rings on hydrazone moiety at position C2 and a 4-iodophenyl at C4 of the thiazole ring gave a promising inhibitory activity especially against Candida albicans and Candida krusei. The most active compounds have been also evaluated for their cytotoxicity and in association with clotrimazole for anti-Candida activity.
- Secci, Daniela,Bizzarri, Bruna,Bolasco, Adriana,Carradori, Simone,D'Ascenzio, Melissa,Rivanera, Daniela,Mari, Emanuela,Polletta, Lucia,Zicari, Alessandra
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experimental part
p. 246 - 253
(2012/08/28)
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- Synthesis and biological evaluation of novel 2,4-disubstituted-1,3- thiazoles as anti-Candida spp. agents
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A new series of [4-(4′-substituted-phenyl)thiazol-2-yl]hydrazine derivatives were synthesized in good yield (86-99%) and characterized by elemental analysis, IR, 1H NMR, and mass spectral studies. The compounds were assayed for their in vitro broad-spectrum antifungal activity, compared to clotrimazole and fluconazole, against 20 clinical isolates of pathogenic Candida spp., representing five different species. The results showed that the presence of heterocyclic or bicyclic rings on hydrazone moiety in position C2 of thiazole revealed a promising selective inhibitory activity especially against Candida albicans and Candida glabrata.
- Chimenti, Franco,Bizzarri, Bruna,Bolasco, Adriana,Secci, Daniela,Chimenti, Paola,Granese, Arianna,Carradori, Simone,D'Ascenzio, Melissa,Lilli, Daniela,Rivanera, Daniela
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experimental part
p. 378 - 382
(2011/02/25)
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- Structural characteristics of thiosemicarbazones as inhibitors of melanogenesis
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A series of thiosemicarbazones 2(e-s) have been synthesized and studied their structure-activity relationship as melanogenesis inhibitor. Among them, (Z)-2-(naphthalen-1-ylmethylene)hydrazinecarbothioamide (2q, >100% inhibition at 10 μM, IC50 = 1.1 μM, C log P = 3.039) showed the strongest inhibitory activity. Regarding their structure-activity relationship, the hydrophobic substituents regardless the position on phenyl ring of benzaldehyde thiosemicarbazones enhance the inhibitory activity. Furthermore, the aromatic group of benzaldehydethiosemicarbazones can be replaced with sterically bulky cyclohexyl. Thus, hydrophobicity of the aryl or alkyl group on hydrazine of thiosemicarbazones is determinant factor for their inhibitory activity in melanogenesis rather than planarity.
- Lee, Ki-Cheul,Thanigaimalai, Pillaiyar,Sharma, Vinay K.,Kim, Min-Seok,Roh, Eunmiri,Hwang, Bang-Yeon,Kim, Youngsoo,Jung, Sang-Hun
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supporting information; experimental part
p. 6794 - 6796
(2011/01/04)
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- Synthesis and anti-Helicobacter pylori activity of 4-(coumarin-3-yl) thiazol-2-ylhydrazone derivatives
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A novel class of coumarin-thiazole conjugated systems (1-31) were synthesized by Hantzsch condensation between α-bromo-3-acetyl coumarin and several thiosemicarbazone intermediates. This scaffold was also evaluated for selective antibacterial activity against 20 isolates of H. pylori clinical strains, including four metronidazole resistant ones.
- Chimenti, Franco,Bizzarri, Bruna,Bolasco, Adriana,Secci, Daniela,Chimenti, Paola,Granese, Arianna,Carradori, Simone,D'Ascenzio, Melissa,Scaltrito, M. Maddalena,Sisto, Francesca
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experimental part
p. 1269 - 1274
(2011/01/05)
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- Synthesis and evaluation of 4-acyl-2-thiazolylhydrazone derivatives for anti-Toxoplasma efficacy in vitro
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A new series of 4-acyl-2-thiazolylhydrazone derivatives was synthesized and screened for its in vitro activity against Toxoplasma gondii. We evaluated parasite growth inhibition and cytotoxicity, inhibition of replication, and inhibition of parasite invasion of host cells. The biological results indicated that some substances had an antiproliferative effect against intracellular T. gondii tachyzoites cultivated in vitro.
- Chimenti, Franco,Bizzarri, Bruna,Bolasco, Adriana,Secci, Daniela,Chimenti, Paola,Carradori, Simone,Granese, Arianna,Rivanera, Daniela,Frishberg, Nathan,Bordón, Claudia,Jones-Brando, Lorraine
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supporting information; experimental part
p. 4574 - 4577
(2010/02/16)
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