143 research outputs found
Use of the 4-hydroxy-triazole moiety as a bioisosteric tool in the development of selective ligands for subtypes AMPA receptor
6-Cyclohexylmethoxy-5-(cyano-NNO-azoxy)pyrimidine-4-amine: A new scaffold endowed with potent CDK2 inhibitory activity
Furazan and furoxan sulfonamides are strong α-carbonic anhydrase inhibitors and potential antiglaucoma agents
The Novel hDHODH Inhibitor MEDS433 Prevents Influenza Virus Replication by Blocking Pyrimidine Biosynthesis
The pharmacological management of influenza virus (IV) infections still poses a series of challenges due to the limited anti-IV drug arsenal. Therefore, the development of new anti-influenza agents effective against antigenically different IVs is therefore an urgent priority. To meet this need, host-targeting antivirals (HTAs) can be evaluated as an alternative or complementary approach to current direct-acting agents (DAAs) for the therapy of IV infections. As a contribution to this antiviral strategy, in this study, we characterized the anti-IV activity of MEDS433, a novel small molecule inhibitor of the human dihydroorotate dehydrogenase (hDHODH), a key cellular enzyme of the de novo pyrimidine biosynthesis pathway. MEDS433 exhibited a potent antiviral activity against IAV and IBV replication, which was reversed by the addition of exogenous uridine and cytidine or the hDHODH product orotate, thus indicating that MEDS433 targets notably hDHODH activity in IV-infected cells. When MEDS433 was used in combination either with dipyridamole (DPY), an inhibitor of the pyrimidine salvage pathway, or with an anti-IV DAA, such as N(4)-hydroxycytidine (NHC), synergistic anti-IV activities were observed. As a whole, these results indicate MEDS433 as a potential HTA candidate to develop novel anti-IV intervention approaches, either as a single agent or in combination regimens with DAAs
Heterocyclic ring cleavage upon collision-induced dissociation of deprotonated 3-hydroxy-1,2,5-oxadiazoles (3-hydroxyfurazans)
Influence of Storage Temperature on Radiochemical Purity of 99mTc-Radiopharmaceuticals
The influence of effective room temperature on the radiochemical purity of
99mTc-radiopharmaceuticals was reported. This study was born from the observation that in
the isolators used for the preparation of the 99mTc-radiopharmaceuticals the temperatures can
be higher than those reported in the commercial illustrative leaflets of the kits. This is due,
in particular, to the small size of the work area, the presence of instruments for heating, the continuous
activation of air filtration, in addition to the fact that the environment of the isolator used for the
99mTc-radiopharmaceuticals preparation and storage is completely isolated and not conditioned.
A total of 244 99mTc-radiopharmaceutical preparations (seven different types) have been tested
and the radiochemical purity was checked at the end of preparation and until the expiry time.
Moreover, we found that the mean temperature into the isolator was significantly higher than 25 C,
the temperature, in general, required for the preparation and storage of 99mTc-radiopharmaceuticals.
Results confirmed the radiochemical stability of radiopharmaceutical products. However, as required
in the field of quality assurance, the impact that different conditions than those required by the
manufacturer on the radiopharmaceuticals quality have to be verified before human administration
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