Dihydropyridines as potential α-amylase and α-glucosidase inhibitors: Synthesis, in vitro and in silico studies

• Published in: Bioorganic chemistry 2020-03, Vol.96, p.103581, Article 103581
• Main Authors: Yousuf, Hina, Shamim, Shahbaz, Khan, Khalid Mohammed, Chigurupati, Sridevi, Kanwal, Hameed, Shehryar, Khan, Muhammad Naseem, Taha, Muhammad, Arfeen, Minhajul
• Format: Article
• Language: English
• Subjects: alpha-Amylases - antagonists & inhibitors; Computer Simulation; Dihydropyridine; Dihydropyridines - chemical synthesis; Dihydropyridines - chemistry; Dihydropyridines - pharmacology; Enzyme Inhibitors - chemical synthesis; Enzyme Inhibitors - chemistry; Enzyme Inhibitors - pharmacology; Glycoside Hydrolase Inhibitors - chemical synthesis; Glycoside Hydrolase Inhibitors - chemistry; Glycoside Hydrolase Inhibitors - pharmacology; In silico studies; In vitro; In Vitro Techniques; Spectrum Analysis - methods; Structure-Activity Relationship; Structure-activity relationship (SAR); Synthesis; α-amylase; α-glucosidase
• ISSN: 0045-2068; 1090-2120
• DOI: 10.1016/j.bioorg.2020.103581

[Display omitted] •Dihydropyridines (1–31) were designed and synthesized.•The synthetic molecules were screened for α-amylase and α-glucosidase inhibitory activities.•Limited structure-activity relationship was developed based on the different substituent patterns on aryl part.•In silico studies were performed to confirm the binding interactions of synthetic molecules with the enzyme active site.•This study had identified potential urease inhibitors which can be used as lead molecules for further studies. Dihydropyridine derivatives 1–31 were synthesized via one-pot solvent free condition and screened for in vitro against α-amylase and α-glucosidase enzyme. The synthetic derivatives 1–31 showed good α-amylase inhibition in the range of IC50 = 2.21 ± 0.06–9.97 ± 0.08 µM, as compared to the standard drug acarbose (IC50 = 2.01 ± 0.1 µM) and α-glucosidase inhibition in the range of IC50 = 2.31 ± 0.09–9.9 ± 0.1 µM as compared to standard acarbose (IC50 = 2.07 ± 0.1 µM), respectively. To determine the mode of binding interactions of synthetic molecules with active sites of enzyme, molecular docking studies were also performed. Different spectroscopic techniques such as 1H, 13C NMR, EI-MS, and HREI-MS were used to characterize all the synthetic compounds.