Vol.:(0123456789) 1 3 Chemical Papers https://doi.org/10.1007/s11696-019-00999-0 ORIGINAL PAPER Synthesis and biological evaluation of 2‑(2‑methyl‑1H‑pyrrol‑3‑yl)‑2‑oxo‑N‑(pyridine‑3‑yl) acetamide derivatives: in vitro α‑glucosidase inhibition, and kinetic and molecular docking study Tadesse Bekele Tafesse 1,2,3  · Ebrahim Saeedian Moghadam 2  · Mohammed Hussen Bule 1,2,4  · Neda Abadian 5  · Mohammad Abdollahi 6  · Mohammad Ali Faramarzi 5  · Mohsen Amini 2 Received: 31 March 2019 / Accepted: 12 November 2019 © Institute of Chemistry, Slovak Academy of Sciences 2019 Abstract One of the therapeutic approaches in the management of type 2 diabetes is delaying the glucose absorption through α-glucosidase enzyme inhibition, which can reduce the occurrence of postprandial hyperglycemia. Based on this thought, a series of novel chloro-substituted 2-(2-methyl-1-phenyl-1H-pyrrol-3-yl)-2-oxo-N-(pyridin-3-yl) acetamide derivatives 5a–i were synthesized and their α-glucosidase inhibitory activities were evaluated. All the synthesized compounds have shown moderate to excellent in vitro α-glucosidase inhibitory activity with IC 50 values in the range of 111–673 µM) as compared to acarbose, the standard drug (750 ± 9 µM). Compound 5e (111 ± 12 µM), among the series, was the most potent inhibitor of α-glucosidase in a competitive mode of action based on the kinetic study. The molecular docking study of compounds 5e and 5a revealed that they have a lower free binding energy (− 4.27 kcal/mol and − 3.17 kcal/mol, respectively) than acarbose (− 2.47 kcal/mol), which indicates that the target compound binds more easily to the enzyme than acarbose does. The outcomes from the molecular docking studies supported the results obtained from the in vitro assay. In conclusion, the overall results of our study reveal that the synthesized compounds could be a potential candidate in the search for novel α-glucosidase inhibitors to manage postprandial hyperglycemia incidence. Keywords α-Glucosidase activity · Docking · Kinetic study · Synthesis · Pyrrole Introduction Diabetes mellitus (DM) is a chronic progressive metabolic disease worldwide due to carbohydrate, fat, and protein metabolism that is characterized by hyperglycemia result- ing from defects of insulin secretion, insulin action, and/or Electronic supplementary material The online version of this article (https://doi.org/10.1007/s11696-019-00999-0) contains supplementary material, which is available to authorized users. * Mohammad Ali Faramarzi faramarz@tums.ac.ir * Mohsen Amini moamini@tums.ac.ir 1 Department of Medicinal Chemistry, Faculty of Pharmacy, Tehran University of Medical Sciences-International Campus (IC-TUMS), Tehran, Iran 2 Department of Medicinal Chemistry, Faculty of Pharmacy, Drug Design and Development Research Center, The Institute of Pharmaceutical Sciences (TIPS), Tehran University of Medical Sciences, Tehran, Iran 3 School of Pharmacy, College of Health & Medical Sciences, Haramaya University, Harar, Ethiopia 4 Department of Pharmacy, College of Medicine and Health Sciences, Ambo University, Ambo, Ethiopia 5 Department of Pharmaceutical Biotechnology, Faculty of Pharmacy and The Institute of Pharmaceutical Sciences, Tehran University of Medical Sciences, Tehran, Iran 6 Department of Pharmacology and Toxicology, Faculty of Pharmacy and The Institute of Pharmaceutical Sciences, Tehran University of Medical Sciences, Tehran, Iran