- Elucidation of the structure of the antineoplastic agents, 2 formylpyridine and 1 formylisoquinoline thiosemicarbazones
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The geometrical isomers of the antineoplastic agents 2 formylpyridine and 1 formylisoquinoline thiosemicarbazones were synthesized and their structure was studied by spectroscopic methods. It was found that the compounds previously described in the litera
- Antonini,Claudi,Franchetti,Grifantini,Martelli
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- New hydrazinothiazole derivatives of usnic acid as potent TDP1 inhibitors
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Tyrosyl-DNA phosphodiesterase 1 (Tdp1) is a promising therapeutic target in cancer therapy. Combination chemotherapy using Tdp1 inhibitors as a component can potentially improve therapeutic response to many chemotherapeutic regimes. A new set of usnic acid derivatives with hydrazonothiazole pharmacophore moieties were synthesized and evaluated as Tdp1 inhibitors. Most of these compounds were found to be potent inhibitors with IC50 values in the low nanomolar range. The activity of the compounds was verified by binding experiments and supported by molecular modeling. The ability of the most effective inhibitors, used at non-toxic concentrations, to sensitize tumors to the anticancer drug topotecan was also demonstrated. The order of administration of the inhibitor and topotecan on their synergistic effect was studied, suggesting that prior or simultaneous introduction of the inhibitor with topotecan is the most effective.
- Filimonov, Aleksander S.,Chepanova, Arina A.,Luzina, Olga A.,Zakharenko, Alexandra L.,Zakharova, Olga D.,Ilina, Ekaterina S.,Dyrkheeva, Nadezhda S.,Kuprushkin, Maxim S.,Kolotaev, Anton V.,Khachatryan, Derenik S.,Patel, Jinal,Leung, Ivanhoe K.H.,Chand, Raina,Ayine-Tora, Daniel M.,Reynisson, Johannes,Volcho, Konstantin P.,Salakhutdinov, Nariman F.,Lavrik, Olga I.
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- 4-(3-Nitrophenyl)thiazol-2-ylhydrazone derivatives as antioxidants and selective hMAO-B inhibitors: synthesis, biological activity and computational analysis
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A new series of 4-(3-nitrophenyl)thiazol-2-ylhydrazone derivatives were designed, synthesised, and evaluated to assess their inhibitory effect on the human monoamine oxidase (hMAO) A and B isoforms. Different (un)substituted (hetero)aromatic substituents were linked to N1 of the hydrazone in order to establish robust structure–activity relationships. The results of the biological testing demonstrated that the presence of the hydrazothiazole nucleus bearing at C4 a phenyl ring functionalised at the meta position with a nitro group represents an important pharmacophoric feature to obtain selective and reversible human MAO-B inhibition for the treatment of neurodegenerative disorders. In addition, the most potent and selective MAO-B inhibitors were evaluated in silico as potential cholinesterase (AChE/BuChE) inhibitors and in vitro for antioxidant activities. The results obtained from molecular modelling studies provided insight into the multiple interactions and structural requirements for the reported MAO inhibitory properties.
- Secci, Daniela,Carradori, Simone,Petzer, Anél,Guglielmi, Paolo,D’Ascenzio, Melissa,Chimenti, Paola,Bagetta, Donatella,Alcaro, Stefano,Zengin, Gokhan,Petzer, Jacobus P.,Ortuso, Francesco
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p. 597 - 612
(2019/02/14)
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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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p. 295 - 308
(2016/11/12)
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- Synthesis, NMR structural characterization and molecular modeling of substituted thiosemicarbazones and semicarbazones using DFT calculations to prove the syn/anti isomer formation
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Thiosemicarbazones possessing electron-donating and electron-withdrawing groups were prepared, and their spectral characteristics determined. In all cases, the spectra showed that one isomer was formed, allowing further functionalization to molecules of biological interest. We provide NMR data for some of the thiosemicarbazones and semicarbazones. We also provide evidence that for 2-pyridyl thiosemicarbazone, the syn isomer slowly converts into the anti isomer in dimethyl sulfoxide solvent with first-order kinetics. Molecular modeling and density functional theory calculations confirmed these observations. Copyright
- Venkatachalam,Pierens, Gregory K.,Reutens, David C.
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- 2-Pyridyl thiazoles as novel anti-Trypanosoma cruzi agents: Structural design, synthesis and pharmacological evaluation
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The present work reports on the synthesis, anti-Trypanosoma cruzi activities and docking studies of a novel series of 2-(pyridin-2-yl)-1,3- thiazoles derived from 2-pyridine thiosemicarbazone. The majority of these compounds are potent cruzain inhibitors
- Cardoso, Marcos Veríssimo De Oliveira,Siqueira, Lucianna Rabelo Pessoa De,Silva, Elany Barbosa Da,Costa, Lívia Bandeira,Hernandes, Marcelo Zaldini,Rabello, Marcelo Montenegro,Ferreira, Rafaela Salgado,Da Cruz, Luana Faria,Magalh?es Moreira, Diogo Rodrigo,Pereira, Valéria Rêgo Alves,De Castro, Maria Carolina Accioly Brelaz,Bernhardt, Paul V.,Leite, Ana Cristina Lima
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- Role of Metalation in the Topoisomerase IIα inhibition and antiproliferation activity of a series of α-heterocyclic-N 4-substituted thiosemicarbazones and their Cu(II) complexes
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The topoisomerase-IIα inhibition and antiproliferative activity of α-heterocyclic thiosemicarbazones and their corresponding copper(II) complexes have been investigated. The CuII(thiosemicarbazonato)Cl complexes were shown to catalytically inhi
- Zeglis, Brian M.,Divilov, Vadim,Lewis, Jason S.
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experimental part
p. 2391 - 2398
(2011/06/10)
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- Antiviral agents and methods of treating viral infections
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The present invention relates to methods of treating viral or fungal infections using 3-aminopyridine-2-carboxyaldehyde thiosemicarbazone (3-AP) and 3-amino-4-methylpyridine-2-carboxaldehyde thiosemicarbazone (3-AMP) and its prodrug forms and to pharmaceutical compositions comprising these compounds.
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- Modified prodrug forms of AP/AMP
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The present invention relates to compounds according to the structure: Where R is H or CH3; R2 is phosphate which can be free acid or salt; R3 is H, F, Cl, Br, I, OCH3, OCF3, CF3 or a C1-C3 alkyl group; R4 is H, F, Cl, Br, I, OCH3, OCF3 or CF3; and R5 and R6 are each independently H, F, Cl, Br, I, OCH3, OCF3 or CF3, with the proviso that when any two of R3, R4, R5 or R6 are other than H, the other two of R3, R4, R5 or R6 are H which may be used to treat neoplasia, including cancer.
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