Design, synthesis, in vitro, and in silico biological evaluations of coumarin-indole hybrids as new anti-α-glucosidase agents
Davood Rezapour Niri, Mohammad Hosein Sayahi, Somayeh Behrouz, Ali Moazzam, Somayeh Mojtabavi, Mohammad Ali Faramarzi, Bagher Larijani, Hossein Rastegar, Maryam Mohammadi‐Khanaposhtani, Mohammad Mahdavi
Abstract
BACKGROUND: A series of coumarin-indole hybrids was synthesized as the new α-glucosidase inhibitors. The title hybrids were considered as α-glucosidase inhibitors because had two active pharmacophores against α-glucosidase: coumarin and indole. METHODS: The thirteen various derivatives 4a-m were synthesized, purified, and fully characterized. These compounds were evaluated against α-glucosidase in vitro and in silico. In silico pharmacokinetic studies of the most potent compounds were also performed. RESULTS: Most of the title compounds exhibited high anti-α-glucosidase activity in comparison to standard drug acarbose. In particular, the phenoxy derivative 4d namely 3-((1H-indol-3-yl)(3-phenoxyphenyl)methyl)-4-hydroxy-2H-chromen-2-one showed promising activity. This compound is a competitive inhibitor against α-glucosidase and showed the lowest binding energy at the α-glucosidase active site in comparison to other potent synthesized compounds and acarbose. CONCLUSION: Compound 4d can be a lead compound for further structural development to obtain effective and potent α-glucosidase inhibitors.