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

被引:4
作者
Mahnashi, Mater H. [1 ]
Alam, Waqas [2 ]
Huneif, Mohammed A. [3 ]
Abdulwahab, Alqahtani [3 ]
Alzahrani, Mohammed Jamaan [3 ]
Alshaibari, Khaled S. [3 ]
Rashid, Umar [4 ]
Sadiq, Abdul [5 ]
Jan, Muhammad Saeed [6 ]
机构
[1] Najran Univ, Coll Pharm, Dept Pharmaceut Chem, Najran 55461, Saudi Arabia
[2] Abdul Wali Khan Univ Mardan, Dept Pharm, Mardan 23200, Pakistan
[3] Najran Univ, Med Coll, Pediat Dept, Najran 55461, Saudi Arabia
[4] COMSATS Univ Islamabad, Dept Chem, Abbottabad 22060, Pakistan
[5] Univ Malakand, Dept Pharm, Chakdara 18800, Pakistan
[6] Bacha Khan Univ, Dept Pharm, Chakdara 24420, Pakistan
来源
MOLECULES | 2023年 / 28卷 / 04期
关键词
succinimide; diabetes; antioxidant; histopathology; acute toxicity; ANTIOXIDANT; PRODUCTS;
D O I
10.3390/molecules28041589
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
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 alpha-amylase, alpha-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 mu M. 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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页数:16
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