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- Title
Exploration of Succinimide Derivative as a Multi-Target, Anti-Diabetic Agent: In Vitro and In Vivo Approaches.
- Authors
Mahnashi, Mater H.; Alam, Waqas; Huneif, Mohammed A.; Abdulwahab, Alqahtani; Alzahrani, Mohammed Jamaan; Alshaibari, Khaled S.; Rashid, Umar; Sadiq, Abdul; Jan, Muhammad Saeed
- Abstract
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 IC50 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.
- Subjects
HYPOGLYCEMIC agents; SUCCINIMIDES; PROTEIN-tyrosine phosphatase; CD26 antigen; PHOSPHOPROTEIN phosphatases
- Publication
Molecules, 2023, Vol 28, Issue 4, p1589
- ISSN
1420-3049
- Publication type
Article
- DOI
10.3390/molecules28041589