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1.
Front Hum Neurosci ; 18: 1342931, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38681742

RESUMEN

Objectives: The auditory spatial processing abilities mature throughout childhood and degenerate in older adults. This study aimed to compare the differences in onset cortical auditory evoked potentials (CAEPs) and location-evoked acoustic change complex (ACC) responses among children, adults, and the elderly and to investigate the impact of aging and development on ACC responses. Design: One hundred and seventeen people were recruited in the study, including 57 typically-developed children, 30 adults, and 30 elderlies. The onset-CAEP evoked by white noise and ACC by sequential changes in azimuths were recorded. Latencies and amplitudes as a function of azimuths were analyzed using the analysis of variance, Pearson correlation analysis, and multiple linear regression model. Results: The ACC N1'-P2' amplitudes and latencies in adults, P1'-N1' amplitudes in children, and N1' amplitudes and latencies in the elderly were correlated with angles of shifts. The N1'-P2' and P2' amplitudes decreased in the elderly compared to adults. In Children, the ACC P1'-N1' responses gradually differentiated into the P1'-N1'-P2' complex. Multiple regression analysis showed that N1'-P2' amplitudes (R2 = 0.33) and P2' latencies (R2 = 0.18) were the two most variable predictors in adults, while in the elderly, N1' latencies (R2 = 0.26) explained most variances. Although the amplitudes of onset-CAEP differed at some angles, it could not predict angle changes as effectively as ACC responses. Conclusion: The location-evoked ACC responses varied among children, adults, and the elderly. The N1'-P2' amplitudes and P2' latencies in adults and N1' latencies in the elderly explained most variances of changes in spatial position. The differentiation of the N1' waveform was observed in children. Further research should be conducted across all age groups, along with behavioral assessments, to confirm the relationship between aging and immaturity in objective ACC responses and poorer subjective spatial performance. Significance: ACCs evoked by location changes were assessed in adults, children, and the elderly to explore the impact of aging and development on these differences.

3.
Med Chem ; 15(7): 801-812, 2019.
Artículo en Inglés | MEDLINE | ID: mdl-30411688

RESUMEN

BACKGROUND: Clinical drugs for herpesvirus exhibit high toxicity and suffer from significant drug resistance. The development of new, effective, and safe anti-herpesvirus agents with different mechanisms of action is greatly required. OBJECTIVE: Novel inhibitors against herpesvirus with different mechanisms of action from that of clinical drugs. METHODS: A series of novel 5-(benzylamino)-1H-1,2,3-triazole-4-carboxamides were efficiently synthesized and EC50 values against Human Cytomegalovirus (HCMV), Varicella-Zoster Virus (VZV) and Herpes Simplex Virus (HSV) were evaluated in vitro. RESULTS: Some compounds present antiviral activity. Compounds 5s and 5t are potent against both HCMV and VZV. Compounds 5m, 5n, 5s, and 5t show similar EC50 values against both TK+ and TK- VZV strains. CONCLUSION: 5-(Benzylamino)-1H-1, 2,3-triazole-4-carboxamides are active against herpesviruses and their activity is remarkably affected by the nature and the position of substituents in the benzene ring. The results indicate that these derivatives are independent of the viral thymidine kinase (TK) for activation, which is indispensable for current drugs. Their mechanisms of action may differ from those of the clinic anti-herpesvirus drugs.


Asunto(s)
Antivirales/farmacología , Citomegalovirus/efectos de los fármacos , Herpesvirus Humano 3/efectos de los fármacos , Triazoles/farmacología , Antivirales/síntesis química , Antivirales/química , Células Cultivadas , Relación Dosis-Respuesta a Droga , Fibroblastos/efectos de los fármacos , Humanos , Pruebas de Sensibilidad Microbiana , Estructura Molecular , Relación Estructura-Actividad , Triazoles/síntesis química , Triazoles/química
4.
Med Chem ; 13(5): 453-464, 2017.
Artículo en Inglés | MEDLINE | ID: mdl-28290250

RESUMEN

BACKGROUND: All of the clinical drugs for herpesvirus infections exhibit high toxicity and suffer from significant drug-resistantance. There is a great need for the development of new, effective, and safe anti-herpesvirus agents with different mechanisms of action. METHODS: A series of novel 5-(benzylthio)-1H-1,2,3-triazole-4-carboxamides were efficiently synthesized and EC50 values against human cytomegalovirus (HCMV), varicella-zoster virus (VZV) and herpes simplex virus (HSV) were evaluated in vitro. RESULTS: Some compounds possess antiviral activity. Compound 7f exhibits promising inhibitory activity against both HCMV and VZV. Our results also indicate that these derivatives are independent of the viral thymidine kinase (TK) for activation, which is indispensable for current drugs. CONCLUSION: 4,5-Bissubstiuted triazoles are active against herpesviruses and the nature and the position of substituents in the benzene ring remarkably affect their activity, such as bromo, cyano and cyanovynil substituents. Future studies should be undertaken to investigate the mechanism of action of these compounds.


Asunto(s)
Antivirales/farmacología , Citomegalovirus/efectos de los fármacos , Herpesvirus Humano 3/efectos de los fármacos , Triazoles/farmacología , Aciclovir/farmacología , Antivirales/síntesis química , Bromodesoxiuridina/análogos & derivados , Bromodesoxiuridina/farmacología , Cidofovir , Citosina/análogos & derivados , Citosina/farmacología , Ganciclovir/farmacología , Herpesvirus Humano 1/efectos de los fármacos , Herpesvirus Humano 2/efectos de los fármacos , Organofosfonatos/farmacología , Timidina Quinasa/metabolismo , Triazoles/síntesis química
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