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Zinc(II) Complex wi...
Zinc(II) Complex with Pyrazolone-Based Hydrazones is Strongly Effective against Trypanosoma brucei Which Causes African Sleeping Sickness
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- Marchetti, Fabio (författare)
- Chemistry Interdisciplinary Project (CHIP), School of Science and Technology, University of Camerino, via Madonna delle Carceri, Macerata, Camerino, Italy
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- Tombesi, Alessia (författare)
- Chemistry Interdisciplinary Project (CHIP), School of Pharmacy, University of Camerino, via Madonna delle Carceri, Macerata, Camerino, Italy
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- Di Nicola, Corrado (författare)
- Chemistry Interdisciplinary Project (CHIP), School of Science and Technology, University of Camerino, via Madonna delle Carceri, Macerata, Camerino, Italy
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- Pettinari, Riccardo (författare)
- Chemistry Interdisciplinary Project (CHIP), School of Pharmacy, University of Camerino, via Madonna delle Carceri, Macerata, Camerino, Italy
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- Verdicchio, Federico (författare)
- Chemistry Interdisciplinary Project (CHIP), School of Pharmacy, University of Camerino, via Madonna delle Carceri, Macerata, Camerino, Italy
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- Crispini, Alessandra (författare)
- MAT-InLAB, Dipartimento di Chimica e Tecnologie Chimiche, Università della Calabria, Cosenza, Arcavacata di Rende, Italy
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- Scarpelli, Francesca (författare)
- MAT-InLAB, Dipartimento di Chimica e Tecnologie Chimiche, Università della Calabria, Cosenza, Arcavacata di Rende, Italy
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- Baldassarri, Cecilia (författare)
- Chemistry Interdisciplinary Project (CHIP), School of Pharmacy, University of Camerino, via Madonna delle Carceri, Macerata, Camerino, Italy
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- Marangoni, Elisa (författare)
- Chemistry Interdisciplinary Project (CHIP), School of Pharmacy, University of Camerino, via Madonna delle Carceri, Macerata, Camerino, Italy
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- Hofer, Anders (författare)
- Umeå universitet,Institutionen för medicinsk kemi och biofysik
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- Galindo, Agustín (författare)
- Departamento de Química Inorganíca, Facultad de Química, Universidad de Sevilla, Aptdo 1203, Sevilla, Spain
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- Petrelli, Riccardo (författare)
- Chemistry Interdisciplinary Project (CHIP), School of Pharmacy, University of Camerino, via Madonna delle Carceri, Macerata, Camerino, Italy
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(creator_code:org_t)
- 2022-08-15
- 2022
- Engelska.
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Ingår i: Inorganic Chemistry. - : American Chemical Society (ACS). - 0020-1669 .- 1520-510X. ; 61:34, s. 13561-13575
- Relaterad länk:
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https://doi.org/10.1...
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https://umu.diva-por... (primary) (Raw object)
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https://urn.kb.se/re...
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https://doi.org/10.1...
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Abstract
Ämnesord
Stäng
- Two pyrazolone-based hydrazones H2L′ [in general, H2L′ in detail, H2L1 = 5-methyl-2-phenyl-4-(2-phenyl-1-(2-(4-(trifluoromethyl)phenyl)hydrazineyl)ethyl)-2,4-dihydro-3H-pyrazol-3-one, H2L2 = (Z)-5-methyl-2-phenyl-4-(2-phenyl-1-(2-(pyridin-2-yl)hydrazineyl)ethylidene)-2,4-dihydro-3H-pyrazol-3-one] were reacted with Zn(II) and Cu(II) acceptors affording the complexes [Zn(HL1)2(MeOH)2], [Cu(HL1)2], and [M(HL2)2] (M = Cu or Zn). X-ray and DFT studies showed the free proligands to exist in the N-H,N-H tautomeric form and that in [Zn(HL1)2(MeOH)2], zinc is six-coordinated by the N,O-chelated (HL1) ligand and other two oxygen atoms of coordinated methanol molecules, while [Cu(HL1)2] adopts a square planar geometry with the two (HL1) ligands in anti-conformation. Finally, the [M(HL2)2] complexes are octahedral with the two (HL2) ligands acting as κ-O,N,N-donors in planar conformation. Both the proligands and metal complexes were tested against the parasite Trypanosoma brucei and Balb3T3 cells. The Zn(II) complexes were found to be very powerful, more than the starting proligands, while maintaining a good safety level. In detail, H2L1 and its Zn(II) complex have high selective index (55 and >100, respectively) against T. brucei compared to the mammalian Balb/3T3 reference cells. These results encouraged the researchers to investigate the mechanism of action of these compounds that have no structural relations with the already known drugs used against T. brucei. Interestingly, the analysis of NTP and dNTP pools in T. brucei treated by H2L1 and its Zn(II) complex showed that the drugs had a strong impact on the CTP pools, making it likely that CTP synthetase is the targeted enzyme.
Ämnesord
- NATURVETENSKAP -- Kemi -- Oorganisk kemi (hsv//swe)
- NATURAL SCIENCES -- Chemical Sciences -- Inorganic Chemistry (hsv//eng)
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Marchetti, Fabio
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Tombesi, Alessia
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Di Nicola, Corra ...
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Pettinari, Ricca ...
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Verdicchio, Fede ...
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Crispini, Alessa ...
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Scarpelli, Franc ...
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Baldassarri, Cec ...
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Marangoni, Elisa
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Hofer, Anders
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Galindo, Agustín
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Petrelli, Riccar ...
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