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Therapeutic Study of Cinnamic Acid Derivative for Oxidative Stress Ablation: The Computational and Experimental Answers

This study aimed to examine the therapeutic activity of the cinnamic acid derivative KAD-7 (N′-(2,4-dichlorobenzylidene)-3-(4-methoxyphenyl) acrylohydrazide) on Fe(2+)-induced oxidative hepatic injury via experimental and computational models. In addition, the role of ATPase and ectonucleoside triph...

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Autores principales: Ojo, Oluwafemi Adeleke, Ogunlakin, Akingbolabo Daniel, Maimako, Rotdelmwa Filibis, Gyebi, Gideon Ampoma, Olowosoke, Christopher Busayo, Taiwo, Odunayo Anthonia, Elebiyo, Tobiloba Christiana, Adeniyi, David, David, Bolaji, Iyobhebhe, Matthew, Adetunji, Juliana Bunmi, Ayokunle, Damilare IyinKristi, Ojo, Adebola Busola, Mothana, Ramzi A., Alanzi, Abdullah R.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10648207/
https://www.ncbi.nlm.nih.gov/pubmed/37959844
http://dx.doi.org/10.3390/molecules28217425
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author Ojo, Oluwafemi Adeleke
Ogunlakin, Akingbolabo Daniel
Maimako, Rotdelmwa Filibis
Gyebi, Gideon Ampoma
Olowosoke, Christopher Busayo
Taiwo, Odunayo Anthonia
Elebiyo, Tobiloba Christiana
Adeniyi, David
David, Bolaji
Iyobhebhe, Matthew
Adetunji, Juliana Bunmi
Ayokunle, Damilare IyinKristi
Ojo, Adebola Busola
Mothana, Ramzi A.
Alanzi, Abdullah R.
author_facet Ojo, Oluwafemi Adeleke
Ogunlakin, Akingbolabo Daniel
Maimako, Rotdelmwa Filibis
Gyebi, Gideon Ampoma
Olowosoke, Christopher Busayo
Taiwo, Odunayo Anthonia
Elebiyo, Tobiloba Christiana
Adeniyi, David
David, Bolaji
Iyobhebhe, Matthew
Adetunji, Juliana Bunmi
Ayokunle, Damilare IyinKristi
Ojo, Adebola Busola
Mothana, Ramzi A.
Alanzi, Abdullah R.
author_sort Ojo, Oluwafemi Adeleke
collection PubMed
description This study aimed to examine the therapeutic activity of the cinnamic acid derivative KAD-7 (N′-(2,4-dichlorobenzylidene)-3-(4-methoxyphenyl) acrylohydrazide) on Fe(2+)-induced oxidative hepatic injury via experimental and computational models. In addition, the role of ATPase and ectonucleoside triphosphate diphosphohydrolase (ENTPDase) in the coordination of cellular signals is speculated upon to proffer suitable therapeutics for metabolic stress disorder upon their inhibition. While we know little about therapeutics with flexible dual inhibitors for these protein targets, this study was designed to screen KAD-7’s (N′-(2,4-dichlorobenzylidene)-3-(4-methoxyphenyl) acrylohydrazide) inhibitory potential for both protein targets. We induced oxidative hepatic damage via the incubation of hepatic tissue supernatant with 0.1 mM FeSO(4) for 30 min at 37 °C. We achieved the treatment by incubating the hepatic tissues with KAD-7 under the same conditions. The catalase (CAT), glutathione (GSH), malondialdehyde (MDA), ATPase, and ENTPDase activity were all measured in the tissues. We predicted how the drug candidate would work against ATPase and ENTPDase targets using molecular methods. When hepatic injury was induced, there was a significant decrease in the levels of the GSH, CAT, and ENTPDase (p < 0.05) activities. In contrast, we found a noticeable rise in the MDA levels and ATPase activity. KAD-7 therapy resulted in lower levels of these activities overall (p < 0.05), as compared to the control levels. We found the compound to have a strong affinity for ATPase (−7.1 kcal/mol) and ENTPDase (−7.4 kcal/mol), and a better chemical reactivity than quercetin. It also met all drug-likeness parameters. Our study shows that KAD-7 can protect the liver from damage caused by FeSO(4) by reducing oxidative stress and purinergic actions. Our studies indicate that KAD-7 could be developed as a therapeutic option since it can flexibly inhibit both ATPase and ENTPDase.
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spelling pubmed-106482072023-11-04 Therapeutic Study of Cinnamic Acid Derivative for Oxidative Stress Ablation: The Computational and Experimental Answers Ojo, Oluwafemi Adeleke Ogunlakin, Akingbolabo Daniel Maimako, Rotdelmwa Filibis Gyebi, Gideon Ampoma Olowosoke, Christopher Busayo Taiwo, Odunayo Anthonia Elebiyo, Tobiloba Christiana Adeniyi, David David, Bolaji Iyobhebhe, Matthew Adetunji, Juliana Bunmi Ayokunle, Damilare IyinKristi Ojo, Adebola Busola Mothana, Ramzi A. Alanzi, Abdullah R. Molecules Article This study aimed to examine the therapeutic activity of the cinnamic acid derivative KAD-7 (N′-(2,4-dichlorobenzylidene)-3-(4-methoxyphenyl) acrylohydrazide) on Fe(2+)-induced oxidative hepatic injury via experimental and computational models. In addition, the role of ATPase and ectonucleoside triphosphate diphosphohydrolase (ENTPDase) in the coordination of cellular signals is speculated upon to proffer suitable therapeutics for metabolic stress disorder upon their inhibition. While we know little about therapeutics with flexible dual inhibitors for these protein targets, this study was designed to screen KAD-7’s (N′-(2,4-dichlorobenzylidene)-3-(4-methoxyphenyl) acrylohydrazide) inhibitory potential for both protein targets. We induced oxidative hepatic damage via the incubation of hepatic tissue supernatant with 0.1 mM FeSO(4) for 30 min at 37 °C. We achieved the treatment by incubating the hepatic tissues with KAD-7 under the same conditions. The catalase (CAT), glutathione (GSH), malondialdehyde (MDA), ATPase, and ENTPDase activity were all measured in the tissues. We predicted how the drug candidate would work against ATPase and ENTPDase targets using molecular methods. When hepatic injury was induced, there was a significant decrease in the levels of the GSH, CAT, and ENTPDase (p < 0.05) activities. In contrast, we found a noticeable rise in the MDA levels and ATPase activity. KAD-7 therapy resulted in lower levels of these activities overall (p < 0.05), as compared to the control levels. We found the compound to have a strong affinity for ATPase (−7.1 kcal/mol) and ENTPDase (−7.4 kcal/mol), and a better chemical reactivity than quercetin. It also met all drug-likeness parameters. Our study shows that KAD-7 can protect the liver from damage caused by FeSO(4) by reducing oxidative stress and purinergic actions. Our studies indicate that KAD-7 could be developed as a therapeutic option since it can flexibly inhibit both ATPase and ENTPDase. MDPI 2023-11-04 /pmc/articles/PMC10648207/ /pubmed/37959844 http://dx.doi.org/10.3390/molecules28217425 Text en © 2023 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Ojo, Oluwafemi Adeleke
Ogunlakin, Akingbolabo Daniel
Maimako, Rotdelmwa Filibis
Gyebi, Gideon Ampoma
Olowosoke, Christopher Busayo
Taiwo, Odunayo Anthonia
Elebiyo, Tobiloba Christiana
Adeniyi, David
David, Bolaji
Iyobhebhe, Matthew
Adetunji, Juliana Bunmi
Ayokunle, Damilare IyinKristi
Ojo, Adebola Busola
Mothana, Ramzi A.
Alanzi, Abdullah R.
Therapeutic Study of Cinnamic Acid Derivative for Oxidative Stress Ablation: The Computational and Experimental Answers
title Therapeutic Study of Cinnamic Acid Derivative for Oxidative Stress Ablation: The Computational and Experimental Answers
title_full Therapeutic Study of Cinnamic Acid Derivative for Oxidative Stress Ablation: The Computational and Experimental Answers
title_fullStr Therapeutic Study of Cinnamic Acid Derivative for Oxidative Stress Ablation: The Computational and Experimental Answers
title_full_unstemmed Therapeutic Study of Cinnamic Acid Derivative for Oxidative Stress Ablation: The Computational and Experimental Answers
title_short Therapeutic Study of Cinnamic Acid Derivative for Oxidative Stress Ablation: The Computational and Experimental Answers
title_sort therapeutic study of cinnamic acid derivative for oxidative stress ablation: the computational and experimental answers
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10648207/
https://www.ncbi.nlm.nih.gov/pubmed/37959844
http://dx.doi.org/10.3390/molecules28217425
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