Rojas VCT

References (2)

Title : Design, synthesis, and biological evaluation of new thalidomide-donepezil hybrids as neuroprotective agents targeting cholinesterases and neuroinflammation - Cristancho_2022_RSC.Med.Chem_13_568
Author(s) : Cristancho Ortiz CJ , de Freitas Silva M , Pruccoli L , Fonseca Nadur N , de Azevedo LL , Kummerle AE , Guedes IA , Dardenne LE , Leomil Coelho LF , Guimaraes MJ , da Silva FMR , Castro N , Gontijo VS , Rojas VCT , de Oliveira MK , Vilela FC , Giusti-Paiva A , Barbosa G , Lima LM , Pinheiro GB , Veras LG , Mortari MR , Tarozzi A , Viegas C, Jr.
Ref : RSC Med Chem , 13 :568 , 2022
Abstract : A new series of eight multifunctional thalidomide-donepezil hybrids were synthesized based on the multi-target-directed ligand strategy and evaluated as potential neuroprotective, cholinesterase inhibitors and anti-neuroinflammatory agents against neurodegenerative diseases. A molecular hybridization approach was used for structural design by combining the N-benzylpiperidine pharmacophore of donepezil and the isoindoline-1,3-dione fragment from the thalidomide structure. The most promising compound, PQM-189 (3g), showed good AChE inhibitory activity with an IC(50) value of 3.15 microM, which was predicted by docking studies as interacting with the enzyme in the same orientation observed in the AChE-donepezil complex and a similar profile of interaction. Additionally, compound 3g significantly decreased iNOS and IL-1beta levels by 43% and 39%, respectively, after 24 h of incubation with lipopolysaccharide. In vivo data confirmed the ability of 3g to prevent locomotor impairment and changes in feeding behavior elicited by lipopolysaccharide. Moreover, the PAMPA assay evidenced adequate blood-brain barrier and gastrointestinal tract permeabilities with an Fa value of 69.8%. Altogether, these biological data suggest that compound 3g can treat the inflammatory process and oxidative stress resulting from the overexpression of iNOS and therefore the increase in reactive nitrogen species, and regulate the release of pro-inflammatory cytokines such as IL-1beta. In this regard, compound PQM-189 (3g) was revealed to be a promising neuroprotective and anti-neuroinflammatory agent with an innovative thalidomide-donepezil-based hybrid molecular architecture.
ESTHER : Cristancho_2022_RSC.Med.Chem_13_568
PubMedSearch : Cristancho_2022_RSC.Med.Chem_13_568
PubMedID: 35694691

Title : Perinatal exposure to glyphosate-based herbicides induced neurodevelopmental behaviors impairments and increased oxidative stress in the prefrontal cortex and hippocampus in offspring - de Oliveira_2022_Int.J.Dev.Neurosci__
Author(s) : de Oliveira MAL , Rojas VCT , de Sa JC , de Novais CO , Silva MS , de Almeida Paula HA , Kirsten TB , Bernardi MM , Pinheiro LC , Giusti-Paiva A , Vilela FC
Ref : Int J Developmental Neuroscience , : , 2022
Abstract : Glyphosate is the organophosphate pesticide most widely used in the world. Recent studies correlate exposure to glyphosate and the emergence of neurodevelopmental disorders. Therefore, it was objective to propose a rat model of perinatal exposure to glyphosate-based herbicides (GBH) to study associated neurodevelopmental disorders. Behavioral aspects and brain pathways were assessed in the prepubertal phase. For this, maternal treatment occurred throughout the entire gestation period (from GD0) until weaning on postnatal day 22 (PND 22). Control group received oral gavage with 5 mL/kg of saline per day and GBH group received oral gavage with 50 mg/kg of GBH per day (n = 10 per group). Maternal behavior was evaluated in PND 2-6. Offspring were evaluated for quantification of ultrasonic vocalizations (PND 5); homing behavior test (PND 13); and hole board, social play behavior, open field, and object recognition tests (PND 28-32). Prefrontal cortex and hippocampus of the offspring were processed to evaluate oxidative stress. Maternal exposure to GBH impaired early social communication, olfactory discrimination, social play behavior, and the exploration of objects, in addition to increasing repetitive and stereotyped movements. GBH also increased oxidative stress. Therefore, perinatal GBH exposure induced behavioral and oxidative stress impairments in rats associated with neurodevelopmental disorders. The manifestations found in the offspring are in accordance with symptoms of autism spectrum disorder.
ESTHER : de Oliveira_2022_Int.J.Dev.Neurosci__
PubMedSearch : de Oliveira_2022_Int.J.Dev.Neurosci__
PubMedID: 35750327