In silico docking studies of α-amylase inhibitors from the anti-diabetic plant Leucas ciliata Benth. and an endophyte, Streptomyces longisporoflavus .

In this investigation, potential inhibitors of α-amylase, one of the key regulatory enzymes in diabetes were characterized from the methanolic extract of Leucas ciliata Benth. (Lamiaceae), a traditional medicinal plant of the Western Ghats, southern India and the ethyl acetate extract of Streptomyces longisporoflavus (JX965948), an endophytic actinomycete isolated from the stem fragments of L. ciliata , by Gas Chromatography and Mass Spectroscopy (GC-MS) technique followed by molecular docking studies. Forty-four compounds were detected in the solvent extracts of the host plant and the endophyte, respectively. These compounds were selected as ligands for the receptor α-amylase in the molecular docking studies using PyRx software (0.8 V) for the inhibition of α-amylase activity. The ligands were ranked based on the binding energies ranging between - 3.1 and - 10.1 kcal/mol. Three ligands from the host plant extract, viz., Topotecan (PNo_7), Cathine (PNo_17) and 2,5-dimethoxy-4-(methylsulfonyl)amphetamine (PNo_18), depicted good binding energies of - 5.2 to - 7.8, respectively, whereas seven compounds from the endophyte extract showed binding energies in the range of - 4.7 to - 10.1, respectively. The standard α-amylase inhibitor Acarbose™ depicted binding energy of - 9.2 kcal/mol. All ligands were subjected to lead-likeliness property using Lipinski's rule of five. On the basis of the hydrogen bonding interactions with the receptor, and chemoinformatics analysis for drug-likeliness, one ligand, Topotecan (PNo_7) from the host plant was identified as the potential α-amylase inhibitor. This is the first attempt to identify alkaloid and flavonoid compounds as the α-amylase inhibitors from the host plant and its endophyte simultaneously. The molecular docking analyses presented in this study could lead to the development of potent α-amylase inhibitors helpful in the treatment of diabetes.

Supplementary Information: The online version of this article (10.1007/s13205-020-02547-0) contains supplementary material, which is available to authorized users.