160 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
Use of the furoxan (1,2,5-oxadiazole 2-oxide) system in the design of new NO-donor antioxidant hybrids
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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)
Validation of a GC/MS method for the detection of two quinoline-derived selective androgen receptor modulators in doping control analysis
Application of the arachnoâ„¢ technology inside Educational fields: the introduction of parallel synthesis concepts inside an undergraduated lab
Probing salicylamide bioisosteric replacement in the design of Plasmodium Falciparum dihydroorotate dehydrogenase (pfDHODH) inhibitors
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