Department of Pharmaceutical Chemistry, College of Pharmacy, Najran University, Najran 55461, Saudi Arabia.
Department of Pharmacy, Abdul Wali Khan University Mardan, Mardan 23200, Pakistan.
Molecules. 2023 Feb 7;28(4):1589. doi: 10.3390/molecules28041589.
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 ) was previously isolated from This compound was reacted with -benzylmaleimide to synthesize the targeted compound . The purpose of this research is to exhibit our developed compound 's ability to concurrently inhibit many targets that are responsible for hyperglycemia. Compound 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 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 . After 21 days of examination, the compound activity pattern was found to be effective in experimental mice. Compound 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 , can affect several targets simultaneously, and, finally, we were successful in synthesizing a multi-targeted preclinical therapy.
糖尿病(DM)是当今时代面临的主要挑战之一,是一种危及生命的疾病。先前从 中分离出的 4-羟基-3-甲氧基苯乙酮(化合物 )与 -苄基马来酰亚胺反应,合成了目标化合物 。本研究旨在展示我们开发的化合物同时抑制多种与高血糖有关的靶标的能力。化合物 能够抑制α-淀粉酶、α-葡萄糖苷酶和蛋白酪氨酸磷酸酶 1B。尽管如此,该化合物对二肽基肽酶-4(DPP-4)的体外抑制作用非常突出,IC 值为 0.07µM。此外,通过使用 DPPH 进行抗氧化活性测定,该化合物表现出良好的抗氧化潜力。同样,在体内活性方面,实验小鼠经化合物 处理后被证明是安全的。经过 21 天的检查,发现化合物 在实验小鼠中的作用模式有效。化合物 降低了 STZ 诱导的糖尿病小鼠中总甘油三酯、总胆固醇、AST、ALT、ALP、LDL、BUN 和肌酐的过量峰值。同样,还评估了治疗动物的肾脏、肝脏和胰腺的组织病理学。总的来说,琥珀酰亚胺部分,如化合物 ,可以同时影响多个靶点,最终我们成功合成了一种多靶点的临床前治疗药物。