Novel acyl hydrazide derivatives of polyhydroquinoline as potent anti-diabetic and anti-glycating agents: Synthesis, in vitro α-amylase, α-glucosidase inhibition and anti-glycating activity with molecular docking insights

• Published in: Bioorganic chemistry 2024-09, Vol.150, p.107501, Article 107501
• Main Authors: Ur Rahman, Sajjad, Alam, Aftab, Parveen, Zahida, Zainab, Assad, Mohammad, Adnan Ali Shah, Syed, Rafiq, Huma, Ayaz, Muhammad, Latif, Abdul, Naveed Umar, Muhammad, Ali, Mumtaz, Ahmad, Manzoor
• Format: Article
• Language: English
• Subjects: Acyl hydrazides; ADME; alpha-Amylases - antagonists & inhibitors; alpha-Amylases - metabolism; alpha-Glucosidases - metabolism; Anti-glycation; Antiglycation Agents; Dose-Response Relationship, Drug; Glycoside Hydrolase Inhibitors - chemical synthesis; Glycoside Hydrolase Inhibitors - chemistry; Glycoside Hydrolase Inhibitors - pharmacology; Humans; Hydrazines - chemical synthesis; Hydrazines - chemistry; Hydrazines - pharmacology; Hypoglycemic Agents - chemical synthesis; Hypoglycemic Agents - chemistry; Hypoglycemic Agents - pharmacology; Molecular docking; Molecular Docking Simulation; Molecular Structure; Polyhydroquinoline; Quinolines - chemical synthesis; Quinolines - chemistry; Quinolines - pharmacology; Structure-Activity Relationship; α-amylase; α-glucosidase
• ISSN: 0045-2068; 1090-2120; 1090-2120
• DOI: 10.1016/j.bioorg.2024.107501

[Display omitted] •Synthesis of novel acyl hydrazide derivatives featuring polyhydroquinoline nuclei.•Structural elucidation by means of modern spectroscopic techniques such as, HR-ESI-MS, 1H NMR, and 13C NMR.•Evaluation of the synthesized analogues for their in vitro anti-diabetic and anti-glycating activities.•Molecular docking study. In this study, eleven novel acyl hydrazides derivative of polyhydroquinoline were synthesized, characterized and screened for their in vitro anti-diabetic and anti-glycating activities. Seven compounds 2a, 2d, 2i, 2 h, 2j, 2f, and 2 g exhibited notable α-amylase inhibitory activity having IC50 values from 3.51 ± 2.13 to 11.92 ± 2.30 µM. Similarly, six compounds 2d, 2f, 2 h, 2i, 2j, and 2 g displayed potent α-glucosidase inhibitory activity compared to the standard acarbose. Moreover, eight derivatives 2d, 2 g, 2f, 2j, 2a, 2i, 2 g, and 2e showed excellent anti-glycating activity with IC50 values from 6.91 ± 2.66 to 15.80 ± 1.87 µM when compared them with the standard rutin (IC50 = 22.5 ± 0.90 µM). Molecular docking was carried out to predict the binding modes of all the compounds with α-amylase and α-glucosidase. The docking analysis revealed that most of the compounds established strong interactions with α-amylase and α-glucosidase. All compounds fitted well into the binding pockets of α-amylase and α-glucosidase. Among all compounds 2a and 2f were most potent based on docking score −8.2515 and −7.3949 against α-amylase and α-glucosidase respectively. These results hold promise for the development of novel candidates targeted at controlling postprandial glucose levels in individuals with diabetes.