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Isatin-based benzyloxybenzene derivatives as monoamine oxidase inhibitors with neuroprotective effect targeting neurogenerative disease treatment

Eighteen isatin-based benzyloxybenzaldehyde derivatives from three subseries, ISB, ISFB, and ISBB, were synthesized and their ability to inhibit monoamine oxidase (MAO) was evaluated. The inhibitory activity of all synthesized compounds was found to be more profound against MAO-B than MAO-A. Compoun...

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Autores principales: Benny, Feba, Oh, Jong Min, Kumar, Sunil, Abdelgawad, Mohamed A., Ghoneim, Mohammed M., Abdel-Bakky, Mohamed Sadek, Kukerti, Neelima, Jose, Jobin, Kim, Hoon, Mathew, Bijo
Formato: Online Artículo Texto
Lenguaje:English
Publicado: The Royal Society of Chemistry 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10694828/
http://dx.doi.org/10.1039/d3ra07035b
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author Benny, Feba
Oh, Jong Min
Kumar, Sunil
Abdelgawad, Mohamed A.
Ghoneim, Mohammed M.
Abdel-Bakky, Mohamed Sadek
Kukerti, Neelima
Jose, Jobin
Kim, Hoon
Mathew, Bijo
author_facet Benny, Feba
Oh, Jong Min
Kumar, Sunil
Abdelgawad, Mohamed A.
Ghoneim, Mohammed M.
Abdel-Bakky, Mohamed Sadek
Kukerti, Neelima
Jose, Jobin
Kim, Hoon
Mathew, Bijo
author_sort Benny, Feba
collection PubMed
description Eighteen isatin-based benzyloxybenzaldehyde derivatives from three subseries, ISB, ISFB, and ISBB, were synthesized and their ability to inhibit monoamine oxidase (MAO) was evaluated. The inhibitory activity of all synthesized compounds was found to be more profound against MAO-B than MAO-A. Compound ISB1 most potently inhibited MAO-B with an IC(50) of 0.124 ± 0.007 μM, ensued by ISFB1 (IC(50) = 0.135 ± 0.002 μM). Compound ISFB1 most potently inhibited MAO-A with an IC(50) of 0.678 ± 0.006 μM, ensued by ISBB3 (IC(50) = 0.731 ± 0.028 μM), and had the highest selectivity index (SI) value (55.03). The three sub-parental compounds, ISB1, ISFB1, and ISBB1, had higher MAO-B inhibition than the other derivatives, indicating that the substitutions of the 5-H in the A-ring of isatin diminished the inhibition of MAO-A and MAO-B. Among these, ISB1 (para-benzyloxy group in the B-ring) displayed more significant MAO-B inhibition when compared to ISBB1 (meta-benzyloxy group in the B-ring). ISB1 and ISFB1 were identified to be competitive and reversible MAO-B inhibitors, having K(i) values of 0.055 ± 0.010, and 0.069 ± 0.025 μM, respectively. Furthermore, in the parallel artificial membrane penetration assay, ISB1 and ISFB1 traversed the blood–brain barrier in the in vitro condition. Additionally, the current study found that ISB1 decreased rotenone-induced cell death in SH-SY5Y neuroblastoma cells. In docking and simulation studies, the hydrogen bonding formed by the imino nitrogen in ISB1 and the pi–pi stacking interaction of the phenyl ring in isatin significantly aided in the protein–ligand complex's stability, effectively inhibiting MAO-B. According to these observations, the MAO-B inhibitors ISB1 and ISFB1 were potent, selective, and reversible, making them conceivable therapies for neurological diseases.
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spelling pubmed-106948282023-12-05 Isatin-based benzyloxybenzene derivatives as monoamine oxidase inhibitors with neuroprotective effect targeting neurogenerative disease treatment Benny, Feba Oh, Jong Min Kumar, Sunil Abdelgawad, Mohamed A. Ghoneim, Mohammed M. Abdel-Bakky, Mohamed Sadek Kukerti, Neelima Jose, Jobin Kim, Hoon Mathew, Bijo RSC Adv Chemistry Eighteen isatin-based benzyloxybenzaldehyde derivatives from three subseries, ISB, ISFB, and ISBB, were synthesized and their ability to inhibit monoamine oxidase (MAO) was evaluated. The inhibitory activity of all synthesized compounds was found to be more profound against MAO-B than MAO-A. Compound ISB1 most potently inhibited MAO-B with an IC(50) of 0.124 ± 0.007 μM, ensued by ISFB1 (IC(50) = 0.135 ± 0.002 μM). Compound ISFB1 most potently inhibited MAO-A with an IC(50) of 0.678 ± 0.006 μM, ensued by ISBB3 (IC(50) = 0.731 ± 0.028 μM), and had the highest selectivity index (SI) value (55.03). The three sub-parental compounds, ISB1, ISFB1, and ISBB1, had higher MAO-B inhibition than the other derivatives, indicating that the substitutions of the 5-H in the A-ring of isatin diminished the inhibition of MAO-A and MAO-B. Among these, ISB1 (para-benzyloxy group in the B-ring) displayed more significant MAO-B inhibition when compared to ISBB1 (meta-benzyloxy group in the B-ring). ISB1 and ISFB1 were identified to be competitive and reversible MAO-B inhibitors, having K(i) values of 0.055 ± 0.010, and 0.069 ± 0.025 μM, respectively. Furthermore, in the parallel artificial membrane penetration assay, ISB1 and ISFB1 traversed the blood–brain barrier in the in vitro condition. Additionally, the current study found that ISB1 decreased rotenone-induced cell death in SH-SY5Y neuroblastoma cells. In docking and simulation studies, the hydrogen bonding formed by the imino nitrogen in ISB1 and the pi–pi stacking interaction of the phenyl ring in isatin significantly aided in the protein–ligand complex's stability, effectively inhibiting MAO-B. According to these observations, the MAO-B inhibitors ISB1 and ISFB1 were potent, selective, and reversible, making them conceivable therapies for neurological diseases. The Royal Society of Chemistry 2023-12-04 /pmc/articles/PMC10694828/ http://dx.doi.org/10.1039/d3ra07035b Text en This journal is © The Royal Society of Chemistry https://creativecommons.org/licenses/by-nc/3.0/
spellingShingle Chemistry
Benny, Feba
Oh, Jong Min
Kumar, Sunil
Abdelgawad, Mohamed A.
Ghoneim, Mohammed M.
Abdel-Bakky, Mohamed Sadek
Kukerti, Neelima
Jose, Jobin
Kim, Hoon
Mathew, Bijo
Isatin-based benzyloxybenzene derivatives as monoamine oxidase inhibitors with neuroprotective effect targeting neurogenerative disease treatment
title Isatin-based benzyloxybenzene derivatives as monoamine oxidase inhibitors with neuroprotective effect targeting neurogenerative disease treatment
title_full Isatin-based benzyloxybenzene derivatives as monoamine oxidase inhibitors with neuroprotective effect targeting neurogenerative disease treatment
title_fullStr Isatin-based benzyloxybenzene derivatives as monoamine oxidase inhibitors with neuroprotective effect targeting neurogenerative disease treatment
title_full_unstemmed Isatin-based benzyloxybenzene derivatives as monoamine oxidase inhibitors with neuroprotective effect targeting neurogenerative disease treatment
title_short Isatin-based benzyloxybenzene derivatives as monoamine oxidase inhibitors with neuroprotective effect targeting neurogenerative disease treatment
title_sort isatin-based benzyloxybenzene derivatives as monoamine oxidase inhibitors with neuroprotective effect targeting neurogenerative disease treatment
topic Chemistry
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10694828/
http://dx.doi.org/10.1039/d3ra07035b
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