Abstract
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.
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Acknowledgment
The financial assistance for AJV and the facilities utilized from the Institution of Excellence-Biodiversity, Bioprospecting and Sustainable Development Project, University of Mysore (IOE-UOM), sponsored by the Ministry of Human Resource & Development (MHRD), Government of India is gratefully acknowledged. We thank Prof. Cletus D’Souza, Emeritus Professor (Rtd.), Department of Studies in Biochemistry, University of Mysore, Manasagangotri, Mysore, for his help, and inputs provided for the study. We acknowledge the assistance provided by the Chairmen, Department of Studies in Biotechnology and facilities at the Department of Studies in Botany Manasagangotri, University of Mysore, Karnataka, India.
Funding
This work was supported by the Institution of Excellence (IOE)- Biodiversity for Sustainable Development project, sanctioned by the Ministry of Human-Resource Development (MHRD), Govt. of India with the Grant Number F. No. 8–21/2008/U.I. dt. 19–05-2009.
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The first author contributed the experimental part on the preparation of methanolic extract of L. ciliata leaves and the isolation and molecular characterization of the endophytic actinomycete from plant fragments, as well as writing and compilation of data for the presentation of manuscript. The second author conducted the molecular docking studies of ligands and the receptor for α-amylase inhibition studies. The third author carried out the overall design of the study and the fourth and the corresponding author collected L. ciliata, Benth., from Western Ghats, southern India and the identification of the specimen and the approval of manuscript in final form.
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Akshatha, J.V., SantoshKumar, H.S., Prakash, H.S. et al. In silico docking studies of α-amylase inhibitors from the anti-diabetic plant Leucas ciliata Benth. and an endophyte, Streptomyces longisporoflavus. 3 Biotech 11, 51 (2021). https://doi.org/10.1007/s13205-020-02547-0
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DOI: https://doi.org/10.1007/s13205-020-02547-0