Investigation of the salicylaldehyde thiosemicarbazone scaffold for inhibition of influenza virus PA endonuclease
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| 024 | 7 | 0 | |a 10.1007/s00775-015-1292-0 |2 doi |
| 035 | |a (NATIONALLICENCE)springer-10.1007/s00775-015-1292-0 | ||
| 245 | 0 | 0 | |a Investigation of the salicylaldehyde thiosemicarbazone scaffold for inhibition of influenza virus PA endonuclease |h [Elektronische Daten] |c [Dominga Rogolino, Alessia Bacchi, Laura De Luca, Gabriele Rispoli, Mario Sechi, Annelies Stevaert, Lieve Naesens, Mauro Carcelli] |
| 520 | 3 | |a The influenza virus PA endonuclease is an attractive target for the development of novel anti-influenza virus therapeutics, which are urgently needed because of the emergence of drug-resistant viral strains. Reported PA inhibitors are assumed to chelate the divalent metal ion(s) (Mg2+ or Mn2+) in the enzyme's catalytic site, which is located in the N-terminal part of PA (PA-Nter). In the present work, a series of salicylaldehyde thiosemicarbazone derivatives have been synthesized and evaluated for their ability to inhibit the PA-Nter catalytic activity. Compounds 1-6 have been evaluated against influenza virus, both in enzymatic assays with influenza virus PA-Nter and in virus yield assays in MDCK cells. In order to establish a structure-activity relationship, the hydrazone analogue of the most active thiosemicarbazone has also been evaluated. Since chelation may represent a mode of action of such class of molecules, we studied the interaction of two of them, one with and one without biological activity versus the PA enzyme, towards Mg2+, the ion that is probably involved in the endonuclease activity of the heterotrimeric influenza polymerase complex. The crystal structure of the magnesium complex of the o-vanillin thiosemicarbazone ligand 1 is also described. Moreover, docking studies of PA endonuclease with compounds 1 and 2 were performed, to further analyse the possible mechanism of action of this class of inhibitors. | |
| 540 | |a SBIC, 2015 | ||
| 690 | 7 | |a Influenza virus |2 nationallicence | |
| 690 | 7 | |a Thiosemicarbazone |2 nationallicence | |
| 690 | 7 | |a Endonuclease |2 nationallicence | |
| 690 | 7 | |a Metal chelation |2 nationallicence | |
| 690 | 7 | |a Antiviral |2 nationallicence | |
| 700 | 1 | |a Rogolino |D Dominga |u Dipartimento di Chimica, Università di Parma, Parco Area delle Scienze 17/A, 43124, Parma, Italy |4 aut | |
| 700 | 1 | |a Bacchi |D Alessia |u Dipartimento di Chimica, Università di Parma, Parco Area delle Scienze 17/A, 43124, Parma, Italy |4 aut | |
| 700 | 1 | |a De Luca |D Laura |u Dipartimento di Scienze del Farmaco e Prodotti per la Salute, Università di Messina, Polo Universitario SS. Annunziata, 98158, Messina, Italy |4 aut | |
| 700 | 1 | |a Rispoli |D Gabriele |u Dipartimento di Chimica, Università di Parma, Parco Area delle Scienze 17/A, 43124, Parma, Italy |4 aut | |
| 700 | 1 | |a Sechi |D Mario |u Dipartimento di Chimica e Farmacia, Università di Sassari, Via Vienna 2, 07100, Sassari, Italy |4 aut | |
| 700 | 1 | |a Stevaert |D Annelies |u Rega Institute for Medical Research, KU Leuven, 3000, Louvain, Belgium |4 aut | |
| 700 | 1 | |a Naesens |D Lieve |u Rega Institute for Medical Research, KU Leuven, 3000, Louvain, Belgium |4 aut | |
| 700 | 1 | |a Carcelli |D Mauro |u Dipartimento di Chimica, Università di Parma, Parco Area delle Scienze 17/A, 43124, Parma, Italy |4 aut | |
| 773 | 0 | |t JBIC Journal of Biological Inorganic Chemistry |d Springer Berlin Heidelberg |g 20/7(2015-10-01), 1109-1121 |x 0949-8257 |q 20:7<1109 |1 2015 |2 20 |o 775 | |
| 856 | 4 | 0 | |u https://doi.org/10.1007/s00775-015-1292-0 |q text/html |z Onlinezugriff via DOI |
| 898 | |a BK010053 |b XK010053 |c XK010000 | ||
| 900 | 7 | |a Metadata rights reserved |b Springer special CC-BY-NC licence |2 nationallicence | |
| 908 | |D 1 |a research-article |2 jats | ||
| 949 | |B NATIONALLICENCE |F NATIONALLICENCE |b NL-springer | ||
| 950 | |B NATIONALLICENCE |P 856 |E 40 |u https://doi.org/10.1007/s00775-015-1292-0 |q text/html |z Onlinezugriff via DOI | ||
| 950 | |B NATIONALLICENCE |P 700 |E 1- |a Rogolino |D Dominga |u Dipartimento di Chimica, Università di Parma, Parco Area delle Scienze 17/A, 43124, Parma, Italy |4 aut | ||
| 950 | |B NATIONALLICENCE |P 700 |E 1- |a Bacchi |D Alessia |u Dipartimento di Chimica, Università di Parma, Parco Area delle Scienze 17/A, 43124, Parma, Italy |4 aut | ||
| 950 | |B NATIONALLICENCE |P 700 |E 1- |a De Luca |D Laura |u Dipartimento di Scienze del Farmaco e Prodotti per la Salute, Università di Messina, Polo Universitario SS. Annunziata, 98158, Messina, Italy |4 aut | ||
| 950 | |B NATIONALLICENCE |P 700 |E 1- |a Rispoli |D Gabriele |u Dipartimento di Chimica, Università di Parma, Parco Area delle Scienze 17/A, 43124, Parma, Italy |4 aut | ||
| 950 | |B NATIONALLICENCE |P 700 |E 1- |a Sechi |D Mario |u Dipartimento di Chimica e Farmacia, Università di Sassari, Via Vienna 2, 07100, Sassari, Italy |4 aut | ||
| 950 | |B NATIONALLICENCE |P 700 |E 1- |a Stevaert |D Annelies |u Rega Institute for Medical Research, KU Leuven, 3000, Louvain, Belgium |4 aut | ||
| 950 | |B NATIONALLICENCE |P 700 |E 1- |a Naesens |D Lieve |u Rega Institute for Medical Research, KU Leuven, 3000, Louvain, Belgium |4 aut | ||
| 950 | |B NATIONALLICENCE |P 700 |E 1- |a Carcelli |D Mauro |u Dipartimento di Chimica, Università di Parma, Parco Area delle Scienze 17/A, 43124, Parma, Italy |4 aut | ||
| 950 | |B NATIONALLICENCE |P 773 |E 0- |t JBIC Journal of Biological Inorganic Chemistry |d Springer Berlin Heidelberg |g 20/7(2015-10-01), 1109-1121 |x 0949-8257 |q 20:7<1109 |1 2015 |2 20 |o 775 | ||