Elucidating the α-amylase inhibitory activity of phytochemicals from Artocarpus altilis: An in silico and in vitro approach.

• Prenylated flavonoids from Artocarpus altilis inhibits alpha amylase. • Prenylated flavonoids from Artocarpus altilis gave good binding energy against alpha amylase. • In vitro assay showed 3-Hydroxycudraflavone demonstrated good alpha amylase inhibitory efficacy. • 6,7-(2,2-dimethylpyrano)-5,2ʹ4ʹ,5ʹ-tetrahydroxy-3-prenylflavone inhibits diabetes enzyme. • 6,7-(2,2-dimethylpyrano-3-dihydrogeranyl-2-hydroxyl-3-methyl-5,8-dimethoxyl-γ-benzopyrone inhibited alpha amylase. Diabetes mellitus is a metabolic disease that can be managed effectively by α-amylase inhibition. This study isolated phytochemicals from Artocarpus altilis and evaluated their α-amylase inhibitory potential using computational and in vitro approaches. Barks of A. altilis collected from the wild, were dried, pulverized, and macerated with 50 % EtOH. The extract was defatted and subsequently partitioned into CHCl 3. The CHCl 3 fraction was subjected to repetitive column chromatography over silica, and Sephadex purification to afford Compounds A1, A2 , and A3 which were identified and elucidated using 1H NMR, 13C NMR, 2D-NMR, and HRESIMS spectroscopic techniques. The α-amylase inhibitory activity of isolated compounds was examined using molecular docking, molecular dynamics simulation, MMPBSA, ADMET and in vitro methods. Spectroscopic characterisation and elucidation identified Compounds A1, A2 , and A3 as 6,7-(2,2-dimethylpyrano)-5,2ʹ4ʹ,5ʹ-tetrahydroxy-3-prenylflavone, 3-Hydroxycudraflavone and 6,7-(2,2-dimethylpyrano-3-dihydrogeranyl-2-hydroxyl-3-methyl-5,8-dimethoxyl-γ-benzopyrone respectively. Molecular docking studies revealed that compound A2 exhibited the highest binding affinity (−8.8 kcal/mol) followed by A1 (−8.6 kcal/mol) and A3 (−8.4 kcal/mol), as against acarbose (−7.7 kcal/mol). The same result was replicated in the molecular dynamics simulation and MMPBSA analysis such that A2 gave better binding energy than A1, A3 , and acarbose. Also, the ADMET study showed the phytochemicals possesses good drug-like properties. The in vitro α-amylase inhibitory activity showed that binding energies with α-amylase in the order A2 (IC 50 of 0.030 μM) > A1 (IC 50 of 0.032 μM) > A3 (IC 50 of 0.045 μM) as compared acarbose (0.049) μM. [ABSTRACT FROM AUTHOR]