Akshatha Jaginakere Vasanthkumar, SantoshKumar Hulikal Shivashankara, Prakash Harishchandra Sripathy, Nalini Monnanda Somaiah
Department of Studies in Botany, University of Mysore, Manasagangotri, Mysore, 570 006 Karnataka India.
Department of Biotechnology, Bioscience Complex, Kuvempu University, JnanaSahyadri, Shankaraghatta, 577 451 Shivamogga, Karnataka India.
3 Biotech. 2021 Feb;11(2):51. doi: 10.1007/s13205-020-02547-0. Epub 2021 Jan 11.
In this investigation, potential inhibitors of α-amylase, one of the key regulatory enzymes in diabetes were characterized from the methanolic extract of Benth. (Lamiaceae), a traditional medicinal plant of the Western Ghats, southern India and the ethyl acetate extract of (JX965948), an endophytic actinomycete isolated from the stem fragments of , 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.
The online version of this article (10.1007/s13205-020-02547-0) contains supplementary material, which is available to authorized users.
在本研究中，通过气相色谱和质谱（GC-MS）技术，随后进行分子对接研究，从印度南部西高止山脉的一种传统药用植物——唇形科的薄荷（Benth.）的甲醇提取物以及从薄荷茎段分离得到的内生放线菌（JX965948）的乙酸乙酯提取物中，鉴定出糖尿病关键调节酶之一α-淀粉酶的潜在抑制剂。在宿主植物和内生菌的溶剂提取物中分别检测到44种化合物。在分子对接研究中，使用PyRx软件（0.8 V版）将这些化合物选作受体α-淀粉酶的配体，以抑制α-淀粉酶活性。根据-3.1至-10.1千卡/摩尔的结合能对配体进行排序。宿主植物提取物中的三种配体，即拓扑替康（PNo_7）、去甲伪麻黄碱（PNo_17）和2,5-二甲氧基-4-（甲基磺酰基）苯丙胺（PNo_18），分别表现出良好的结合能，为-5.2至-7.8，而内生菌提取物中的七种化合物的结合能分别在-4.7至-10.1范围内。标准α-淀粉酶抑制剂阿卡波糖™的结合能为-9.2千卡/摩尔。使用Lipinski的五规则对所有配体进行类先导物性质分析。基于与受体的氢键相互作用以及药物相似性的化学信息学分析，宿主植物中的一种配体拓扑替康（PNo_7）被鉴定为潜在的α-淀粉酶抑制剂。这是首次同时从宿主植物及其内生菌中鉴定出生物碱和黄酮类化合物作为α-淀粉酶抑制剂。本研究中呈现的分子对接分析可能会促成有助于治疗糖尿病的强效α-淀粉酶抑制剂的开发。
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