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.
引用
收藏
页数:16
相关论文
共 36 条
  • [21] Insights into one drug, multi-target aspects of polyphenols for diabetes management: in vitro, in vivo, and clinical evidence
    Kannan, Karthika
    George, Jissy Anna
    Sahadevan, Revathy
    Kothari, Manan
    Sadhukhan, Sushabhan
    PHYTOCHEMISTRY REVIEWS, 2024,
  • [22] Novel indole based fused triazole-thiadiazole derivatives as anti-diabetic agents: in vitro and in silico approaches
    Iqbal, Tayyiaba
    Khan, Shoaib
    Hussain, Rafaqat
    Khan, Yousaf
    Shoaib, Khurram
    Rozeenad
    Saeed, Masab
    Darwish, Hany W.
    FUTURE MEDICINAL CHEMISTRY, 2024, 16 (23) : 2475 - 2486
  • [23] Anti-diabetic properties of brewer's spent yeast peptides. In vitro, in silico and ex vivo study after simulated gastrointestinal digestion
    Aquino, Marilin E.
    Drago, Silvina R.
    Sanchez de Medina, Fermin
    Martinez-Augustin, Olga
    Cian, Raul E.
    FOOD & FUNCTION, 2024, 15 (07) : 3778 - 3790
  • [24] Integrating network pharmacology, molecular docking and simulation approaches with machine learning reveals the multi-target pharmacological mechanism of Berberis integerrima against diabetic nephropathy
    Zhang, Xueqin
    Chao, Peng
    Zhang, Lei
    Lu, Jinyu
    Yang, Aiping
    Jiang, Hong
    Lu, Chen
    JOURNAL OF BIOMOLECULAR STRUCTURE & DYNAMICS, 2025, 43 (04) : 2092 - 2108
  • [25] Discovery of novel hybrids of Morpholino-1,3,5-triazine-pyrimidine as an anti-diabetic agent in High-fat, Low-dose Streptozotocin-induced diabetes in Wistar rats: An in-vitro, in-silico and in-vivo study
    Gupta, Akanksha
    Bhat, Hans Raj
    Singh, Udaya Pratap
    JOURNAL OF MOLECULAR STRUCTURE, 2023, 1294
  • [26] Multi target interactions of essential oil nanoemulsion of Cinnamomum travancoricum against diabetes mellitus via in vitro, in vivo and in silico approaches
    Sriramavaratharajan, Venkatraman
    Chellappan, David Raj
    Karthi, Shanmugam
    Ilamathi, Mathialagan
    Murugan, Ramar
    PROCESS BIOCHEMISTRY, 2022, 118 : 190 - 204
  • [27] Green Synthesis and Characterization of Silver Nanoparticles Using Azadirachta indica Seeds Extract: In Vitro and In Vivo Evaluation of Anti-Diabetic Activity
    Rehman, Gauhar
    Umar, Muhammad
    Shah, Nasrullah
    Hamayun, Muhammad
    Ali, Abid
    Khan, Waliullah
    Khan, Arif
    Ahmad, Sajjad
    Alrefaei, Abdulwahed Fahad
    Almutairi, Mikhlid H.
    Moon, Yong-Sun
    Ali, Sajid
    PHARMACEUTICALS, 2023, 16 (12)
  • [28] In vitro (anti-alpha-glucosidase) activity and in vivo anti-diabetic activity of Androsace foliosa (common rock jasmine) in alloxan-induced diabetic BALB/c mice
    Zaheer, Jawad
    Najam-Us-Sayb, Qazi
    Qamar, Misba
    Akram, Muhammad
    EUROPEAN JOURNAL OF INFLAMMATION, 2019, 17
  • [29] In vitro and in vivo anti-diabetic and hepatoprotective effects of edible pods of Parkia roxburghii and quantification of the active constituent by HPLC-PDA
    Sheikh, Yunus
    Maibam, Beebina Chanu
    Talukdar, Narayan Chandra
    Deka, Dibakar Chandra
    Borah, Jagat Chandra
    JOURNAL OF ETHNOPHARMACOLOGY, 2016, 191 : 21 - 28
  • [30] Discovery of Natural Multi-Target Neuraminidase Inhibitors Anti-Influenza Virus from Chinese Medicinal Herbs Containing Coumarin: In Silico and In Vitro Experiments
    Wu, Yidi
    Hu, Jiamin
    Ma, Bei
    Nie, Xiaoning
    Sun, Jiaying
    CHEMISTRYSELECT, 2024, 9 (36):