鉴定levomenthol衍生物作为潜在的 dipeptidyl peptidase-4 抑制剂:与 gliptins 的比较研究
Adebowale A Alade1, Samad A Ahmed1, Somdutt Mujwar2
1Department of Biochemistry, Adekunle Ajasin University, Ondo, Nigeria.
Journal of biomolecular structure & dynamics
|June 1, 2023
概括
研究人员确定了四种新型化合物,它们与DPP4的结合亲和力比gliptins更高,为2型糖尿病 (T2DM) 提供了潜在的新疗法. 这些化合物显示出开发更安全,更有效的抗糖尿病药物的前景.
科学领域:
- 药用化学 医学化学
- 药理学 药理学是指药理学的学科.
- 计算生物学 计算生物学
背景情况:
- 双基化酶-4 (DPP4) 抑制剂对于管理2型糖尿病 (T2DM) 是至关重要的.
- 现有的DPP4抑制剂 (gliptins) 由于副作用和T2DM日益流行而面临局限性.
- 需要一种新的,更安全,更有效的DPP4抑制剂.
研究的目的:
- 选和识别新型DPP4抑制剂,以提高疗效和安全性.
- 为了比较新型化合物的结合亲和力与现有的gliptins.
- 评估潜在候选药物的药物相似性,合成性和毒性.
主要方法:
- 选了1800多种新型化合物.
- 双因素分子对接,以评估与DPP4的结合亲和力.
- 模拟分子动力学以评估复杂的稳定性.
- 对化合物的毒性和药理性质的评估.
主要成果:
- 四种新型化合物对DPP4的结合亲和力比目前的gliptins更高.
- 这些化合物与DPP4活性部位的关键残留物 (GLU205,GLU206,TYR662,TYR666) 相互作用.
- 鉴定到的化合物是类似于药物的,容易合成,与gliptins相比,它们的毒性较低.
结论:
- 这些新型化合物代表了开发下一代DPP4抑制剂的有希望的候选者.
- 这些发现支持对新型抗糖尿病疗法的进一步研究.
- 这些已识别的化合物为T2DM的现有治疗提供了潜在的替代方案.
相关概念视频
Dipeptidyl Peptidase 4 Inhibitors
216
Dipeptidyl peptidase 4 (DPP-4) is a serine protease widely distributed in the body. It's involved in the inactivation of GLP-1 and GIP hormones, which are crucial for insulin regulation. DPP-4 inhibitors, such as sitagliptin (Januvia), saxagliptin (Onglyza), linagliptin (Tradjenta), alogliptin (Nesina), and vildagliptin (Galvus), help increase the proportion of active GLP-1, enhancing insulin secretion. These inhibitors work by competitively binding to DPP-4. This binding causes a...
216
Glucagon-like Receptor Agonists
372
Incretins include glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP), which stimulate insulin secretion post-meals. In type 2 diabetes, GIP's efficacy is reduced, making GLP-1 a viable drug target. GIP originates from preproGIP.
GLP-1, when administered in high doses intravenously, triggers insulin secretion, inhibits glucagon release, slows gastric emptying, reduces food intake, and restores normal insulin secretion. However, its rapid inactivation by...
GLP-1, when administered in high doses intravenously, triggers insulin secretion, inhibits glucagon release, slows gastric emptying, reduces food intake, and restores normal insulin secretion. However, its rapid inactivation by...
372
Oral Hypoglycemic Agents: Glinides
190
Repaglinide (Prandin) and Nateglinide (Starlix), known as glinides, are oral insulin secretagogues that stimulate insulin release from pancreatic β cells by closing the ATP-sensitive potassium channels (KATP channel). Repaglinide controls insulin release from pancreatic β cells by managing potassium efflux. It shares two binding sites with sulfonylureas and also has a unique site, indicating overlapping mechanisms of action. With a rapid onset and a 4-7 hour duration, it effectively...
190
Oral Hypoglycemic Agents: α-Glucosidase Inhibitors
220
α-glucosidase inhibitors, including acarbose (Precose), miglitol (Glyset), and voglibose (Voglib) (primarily available in Asia), are drugs that control blood sugar levels by delaying the digestion of starch and disaccharides. They achieve this by inhibiting α-glucosidase enzymes in the intestine, which slow the absorption of carbohydrates in the intestine, which in turn leads to a prolonged release of the glucoregulatory hormone GLP-1 from intestinal L-cells.
Acarbose and miglitol are...
Acarbose and miglitol are...
220
Oral Hypoglycemic Agents: Biguanides and Glitazones
241
Biguanides, particularly metformin (Glucophage), are insulin sensitizers that enhance glucose uptake, thereby reducing insulin resistance. Unlike sulfonylureas, metformin doesn't prompt insulin secretion, which helps to curb hypoglycemia risk. Metformin is beneficial in treating conditions like polycystic ovary syndrome due to its insulin-resistance reduction capability. The drug's primary action involves curtailing hepatic gluconeogenesis, a significant contributor to high blood...
241
Oral Hypoglycemic Agents: Sulfonylureas
251
Sulfonylureas are oral hypoglycemic agents utilized in treating type 2 diabetes. They are characterized by their unique sulfonylurea chemical structure. The family of sulfonylureas is divided into generations. First-generation sulfonylureas, including tolbutamide (Orinase), chlorpropamide (Diabinese), and tolazamide (Tolinase), trigger insulin release from pancreatic β cells and enhance peripheral tissues' insulin sensitivity. The second-generation members, such as glipizide...
251


