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Exploration of Succinimide Derivative as a Multi-Target, Anti-Diabetic Agent: In Vitro and In Vivo Approaches

Diabetes mellitus (DM) is counted among one of the leading challenges in the recent era, and it is a life-threatening disorder. Compound 4-hydroxy 3-methoxy phenylacetone (compound 1) was previously isolated from Polygonum aviculare. This compound was reacted with N-benzylmaleimide to synthesize the...

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Autores principales: Mahnashi, Mater H., Alam, Waqas, Huneif, Mohammed A., Abdulwahab, Alqahtani, Alzahrani, Mohammed Jamaan, Alshaibari, Khaled S., Rashid, Umar, Sadiq, Abdul, Jan, Muhammad Saeed
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9964140/
https://www.ncbi.nlm.nih.gov/pubmed/36838577
http://dx.doi.org/10.3390/molecules28041589
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author Mahnashi, Mater H.
Alam, Waqas
Huneif, Mohammed A.
Abdulwahab, Alqahtani
Alzahrani, Mohammed Jamaan
Alshaibari, Khaled S.
Rashid, Umar
Sadiq, Abdul
Jan, Muhammad Saeed
author_facet Mahnashi, Mater H.
Alam, Waqas
Huneif, Mohammed A.
Abdulwahab, Alqahtani
Alzahrani, Mohammed Jamaan
Alshaibari, Khaled S.
Rashid, Umar
Sadiq, Abdul
Jan, Muhammad Saeed
author_sort Mahnashi, Mater H.
collection PubMed
description Diabetes mellitus (DM) is counted among one of the leading challenges in the recent era, and it is a life-threatening disorder. Compound 4-hydroxy 3-methoxy phenylacetone (compound 1) was previously isolated from Polygonum aviculare. This compound was reacted with N-benzylmaleimide to synthesize the targeted compound 3. The purpose of this research is to exhibit our developed compound 3’s ability to concurrently inhibit many targets that are responsible for hyperglycemia. Compound 3 was capable of inhibiting α-amylase, α-glucosidase, and protein tyrosine phosphatase 1 B. Even so, outstanding in vitro inhibition was shown by the compound against dipeptidyl peptidase-4 (DPP-4) with an IC(50) value of 0.07 µM. Additionally, by using DPPH in the antioxidant activity, it exhibited good antioxidant potential. Similarly, in the in vivo activity, the experimental mice proved to be safe by treatment with compound 3. After 21 days of examination, the compound 3 activity pattern was found to be effective in experimental mice. Compound 3 decreased the excess peak of total triglycerides, total cholesterol, AST, ALT, ALP, LDL, BUN, and creatinine in the STZ-induced diabetic mice. Likewise, the histopathology of the kidneys, liver, and pancreas of the treated animals was also evaluated. Overall, the succinimde moiety, such as compound 3, can affect several targets simultaneously, and, finally, we were successful in synthesizing a multi-targeted preclinical therapy.
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spelling pubmed-99641402023-02-26 Exploration of Succinimide Derivative as a Multi-Target, Anti-Diabetic Agent: In Vitro and In Vivo Approaches Mahnashi, Mater H. Alam, Waqas Huneif, Mohammed A. Abdulwahab, Alqahtani Alzahrani, Mohammed Jamaan Alshaibari, Khaled S. Rashid, Umar Sadiq, Abdul Jan, Muhammad Saeed Molecules Article Diabetes mellitus (DM) is counted among one of the leading challenges in the recent era, and it is a life-threatening disorder. Compound 4-hydroxy 3-methoxy phenylacetone (compound 1) was previously isolated from Polygonum aviculare. This compound was reacted with N-benzylmaleimide to synthesize the targeted compound 3. The purpose of this research is to exhibit our developed compound 3’s ability to concurrently inhibit many targets that are responsible for hyperglycemia. Compound 3 was capable of inhibiting α-amylase, α-glucosidase, and protein tyrosine phosphatase 1 B. Even so, outstanding in vitro inhibition was shown by the compound against dipeptidyl peptidase-4 (DPP-4) with an IC(50) value of 0.07 µM. Additionally, by using DPPH in the antioxidant activity, it exhibited good antioxidant potential. Similarly, in the in vivo activity, the experimental mice proved to be safe by treatment with compound 3. After 21 days of examination, the compound 3 activity pattern was found to be effective in experimental mice. Compound 3 decreased the excess peak of total triglycerides, total cholesterol, AST, ALT, ALP, LDL, BUN, and creatinine in the STZ-induced diabetic mice. Likewise, the histopathology of the kidneys, liver, and pancreas of the treated animals was also evaluated. Overall, the succinimde moiety, such as compound 3, can affect several targets simultaneously, and, finally, we were successful in synthesizing a multi-targeted preclinical therapy. MDPI 2023-02-07 /pmc/articles/PMC9964140/ /pubmed/36838577 http://dx.doi.org/10.3390/molecules28041589 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
Mahnashi, Mater H.
Alam, Waqas
Huneif, Mohammed A.
Abdulwahab, Alqahtani
Alzahrani, Mohammed Jamaan
Alshaibari, Khaled S.
Rashid, Umar
Sadiq, Abdul
Jan, Muhammad Saeed
Exploration of Succinimide Derivative as a Multi-Target, Anti-Diabetic Agent: In Vitro and In Vivo Approaches
title Exploration of Succinimide Derivative as a Multi-Target, Anti-Diabetic Agent: In Vitro and In Vivo Approaches
title_full Exploration of Succinimide Derivative as a Multi-Target, Anti-Diabetic Agent: In Vitro and In Vivo Approaches
title_fullStr Exploration of Succinimide Derivative as a Multi-Target, Anti-Diabetic Agent: In Vitro and In Vivo Approaches
title_full_unstemmed Exploration of Succinimide Derivative as a Multi-Target, Anti-Diabetic Agent: In Vitro and In Vivo Approaches
title_short Exploration of Succinimide Derivative as a Multi-Target, Anti-Diabetic Agent: In Vitro and In Vivo Approaches
title_sort exploration of succinimide derivative as a multi-target, anti-diabetic agent: in vitro and in vivo approaches
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9964140/
https://www.ncbi.nlm.nih.gov/pubmed/36838577
http://dx.doi.org/10.3390/molecules28041589
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