| Autor: |
Hawash M; Department of Pharmacy, Faculty of Medicine and Health Sciences, An-Najah National University, P403, Nablus 00970, Palestine., Qneibi M; Department of Biomedical Sciences, Faculty of Medicine and Health Sciences, An-Najah National University, P403, Nablus 00970, Palestine., Natsheh H; Department of Pharmacy, Faculty of Medicine and Health Sciences, An-Najah National University, P403, Nablus 00970, Palestine., Mohammed NH; Department of Biomedical Sciences, Faculty of Medicine and Health Sciences, An-Najah National University, P403, Nablus 00970, Palestine., Hamda LA; Department of Biomedical Sciences, Faculty of Medicine and Health Sciences, An-Najah National University, P403, Nablus 00970, Palestine., Kumar A; Biological and Chemical Research Centre, Department of Chemistry, University of Warsaw, ul. Żwirki i Wigury 101, 02-089 Warsaw, Poland., Olech B; Biological and Chemical Research Centre, Department of Chemistry, University of Warsaw, ul. Żwirki i Wigury 101, 02-089 Warsaw, Poland.; Centre of New Technologies, University of Warsaw, ul. S. Banacha 2c, 02-097 Warsaw, Poland., Dominiak PM; Biological and Chemical Research Centre, Department of Chemistry, University of Warsaw, ul. Żwirki i Wigury 101, 02-089 Warsaw, Poland., Bdir S; Department of Biomedical Sciences, Faculty of Medicine and Health Sciences, An-Najah National University, P403, Nablus 00970, Palestine., Bdair M; Department of Biomedical Sciences, Faculty of Medicine and Health Sciences, An-Najah National University, P403, Nablus 00970, Palestine. |
| Abstrakt: |
Parkinson's disease (PD) is a significant health issue because it gradually damages the nervous system. α-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors play a significant role in the development of PD. The current investigation employed hybrid benzodioxole-propanamide (BDZ-P) compounds to get information on AMPA receptors, analyze their biochemical and biophysical properties, and assess their neuroprotective effects. Examining the biophysical characteristics of all the subunits of the AMPA receptor offers insights into the impact of BDZ-P on the desensitization and deactivation rate. It demonstrates a partial improvement in the locomotor capacities in a mouse model of Parkinson's disease. In addition, the in vivo experiment assessed the locomotor activity by utilizing the open-field test. Our findings demonstrated that BDZ-P7 stands out with its remarkable potency, inhibiting the GluA2 subunit nearly 8-fold with an IC 50 of 3.03 μM, GluA1/2 by 7.5-fold with an IC 50 of 3.14 μM, GluA2/3 by nearly 7-fold with an IC 50 of 3.19 μM, and GluA1 by 6.5-fold with an IC 50 of 3.2 μM, significantly impacting the desensitization and deactivation rate of the AMPA receptor. BDZ-P7 showed an in vivo impact of partially reinstating locomotor abilities in a mouse model of PD. The results above suggest that the BDZ-P7 compounds show great promise as top contenders for the development of novel neuroprotective therapies. |
