Machado RP

References (2)

Title : New multifunctional AChE inhibitor drug prototypes protect against Abeta-induced memory deficit - Bellozi_2020_Neurol.Sci_41_451
Author(s) : Bellozi PMQ , Campos AC , Viegas FPD , Silva MF , Machado RP , Vaz SM , Riquiel MM , Carneiro-Junior WO , Lima IVA , Saliba SW , Vaz GN , Viegas C, Jr. , de Oliveira ACP
Ref : Neurol Sci , 41 :451 , 2020
Abstract : Alzheimer's disease (AD) is the most incident neurodegenerative disorder, characterized by accumulation of extracellular amyloid-beta (Abeta), intracellular neurofibrillary tangles, and cognitive impairment. The current available treatments are mainly based on the use of reversible acetylcholinesterase (AChE) inhibitors, which only ameliorate the cognitive deficits. However, it is important to develop disease-modifying drugs with neuroprotective effects in order to hamper the progression of the disease. Here, we describe the effect of four promising new drugs with additional protective characteristics on AD-associated memory changes. C57Bl/6 mice treated with the compounds received an intra-hippocampal injection of Abeta1-40 and were submitted to the novel object recognition test, to evaluate memory recovery. All the compounds prevented memory loss. Compounds PQM-56 (4c) and PQM-67 (4g) showed the best profile of memory recovery, representing potential drug candidates for AD treatment.
ESTHER : Bellozi_2020_Neurol.Sci_41_451
PubMedSearch : Bellozi_2020_Neurol.Sci_41_451
PubMedID: 31506829

Title : Design, synthesis and pharmacological evaluation of N-benzyl-piperidinyl-aryl-acylhydrazone derivatives as donepezil hybrids: Discovery of novel multi-target anti-alzheimer prototype drug candidates - Dias Viegas_2018_Eur.J.Med.Chem_147_48
Author(s) : Dias Viegas FP , de Freitas Silva M , Divino da Rocha M , Castelli MR , Riquiel MM , Machado RP , Vaz SM , Simoes de Lima LM , Mancini KC , Marques de Oliveira PC , Morais EP , Gontijo VS , da Silva FMR , D'Alincourt da Fonseca Pecanha D , Castro NG , Neves GA , Giusti-Paiva A , Vilela FC , Orlandi L , Camps I , Veloso MP , Leomil Coelho LF , Ionta M , Ferreira-Silva GA , Pereira RM , Dardenne LE , Guedes IA , de Oliveira Carneiro Junior W , Quaglio Bellozi PM , Pinheiro de Oliveira AC , Ferreira FF , Pruccoli L , Tarozzi A , Viegas C, Jr.
Ref : Eur Journal of Medicinal Chemistry , 147 :48 , 2018
Abstract : A new series of sixteen multifunctional N-benzyl-piperidine-aryl-acylhydrazones hybrid derivatives was synthesized and evaluated for multi-target activities related to Alzheimer's disease (AD). The molecular hybridization approach was based on the combination, in a single molecule, of the pharmacophoric N-benzyl-piperidine subunit of donepezil, the substituted hydroxy-piperidine fragment of the AChE inhibitor LASSBio-767, and an acylhydrazone linker, a privileged structure present in a number of synthetic aryl- and aryl-acylhydrazone derivatives with significant AChE and anti-inflammatory activities. Among them, compounds 4c, 4d, 4g and 4j presented the best AChE inhibitory activities, but only compounds 4c and 4g exhibited concurrent anti-inflammatory activity in vitro and in vivo, against amyloid beta oligomer (AbetaO) induced neuroinflammation. Compound 4c also showed the best in vitro and in vivo neuroprotective effects against AbetaO-induced neurodegeneration. In addition, compound 4c showed a similar binding mode to donepezil in both acetylated and free forms of AChE enzyme in molecular docking studies and did not show relevant toxic effects on in vitro and in vivo assays, with good predicted ADME parameters in silico. Overall, all these results highlighted compound 4c as a promising and innovative multi-target drug prototype candidate for AD treatment.
ESTHER : Dias Viegas_2018_Eur.J.Med.Chem_147_48
PubMedSearch : Dias Viegas_2018_Eur.J.Med.Chem_147_48
PubMedID: 29421570