Design, synthesis, and α‐glucosidase‐inhibitory activity of phenoxy‐biscoumarin<i>–N</i>‐phenylacetamide hybrids
Samira Ansari, Homa Azizian, Keyvan Pedrood, Ali Yavari, Somayeh Mojtabavi, Mohammad Ali Faramarzi, Shiva Golshani, Samanesadat Hosseini, Mahmood Biglar, Bagher Larijani, Hossein Rastegar, Haleh Hamedifar, Maryam Mohammadi‐Khanaposhtani, Mohammad Mahdavi
Abstract
Abstract Thirteen new phenoxy‐biscoumarin– N ‐phenylacetamide derivatives ( 7a – m ) were designed based on a molecular hybridization approach as new α‐glucosidase inhibitors. These compounds were synthesized with high yields and evaluated in vitro for their inhibitory activity against yeast α‐glucosidase. The obtained results revealed that a significant proportion of the synthesized compounds showed considerable α‐glucosidase‐inhibitory activity in comparison to acarbose as a positive control. Representatively, 2‐(4‐(bis(4‐hydroxy‐2‐oxo‐2 H ‐chromen‐3‐yl)methyl)phenoxy)‐ N ‐(4‐bromophenyl)acetamide ( 7f ), with IC 50 = 41.73 ± 0.38 µM against α‐glucosidase, was around 18 times more potent than acarbose (IC 50 = 750.0 ± 10.0 µM). This compound was a competitive α‐glucosidase inhibitor. Molecular modeling and dynamic simulation of these compounds confirmed the obtained results through in vitro experiments. Prediction of the druglikeness/ADME/toxicity of the compound 7f and comparison with the standard drug acarbose showed that the new compound 7f was probably better than the standard drug in terms of toxicity.