Department of Pharmaceutical Analysis and Medicinal Chemistry, Faculty of Pharmacy, Universitas Padjadjaran, Jl Raya 21.5 Bandung-Sumedang 45363, Indonesia.
Department of Pharmaceutical Technology, School of Pharmaceutical Sciences, Universiti Sains Malaysia, P Pinang 11800, Malaysia.
Molecules. 2020 Feb 13;25(4):821. doi: 10.3390/molecules25040821.
The neuraminidase enzyme (NA) from the influenza virus is responsible for the proliferation and infections of the virus progeny, prompting several efforts to discover and optimize effective neuraminidase inhibitors. The main aim of this study is to discover a new potential neuraminidase inhibitor that comes from leaves (GCL). The bioassay-guided isolation method was performed to obtain lead compounds. The binding interaction of the isolated compounds was predicted by using molecular docking studies. Friedeline (GC1, log > 5.0), two lanastone derivatives (methyl-3α,23-dihydroxy-17,14-friedolanstan-8,14,24-trien-26-oat (GC2) and 24E-3a,9,23-trihydroxy-17,14-friedolanostan-14,24-dien-26-oate (GC3) with Log > 5.0) and catechin (GC4, Log = 1.4) were identified. The inhibitory potency of these four compounds on NA from and HN was found to be as follows: GC4 > GC2 > GC3 > GC1. All compounds exhibited higher inhibitory activity towards NA compared to HN NA. From the molecular docking results, GC4 favorably docked and interacted with Arg118, Arg371, Arg292, Glu276 and Trp178 residues, whilst GC2 interacted with Arg118, Arg371, Arg292, Ile222, Arg224 and Ser246. GC3 interacted with Tyr406 only. GC4 had potent NA inhibition with free energy of binding of -12 kcal/mol. In the enzyme inhibition study, GC4 showed the highest activity with an IC of 60.3 µM and 91.0 µM for NA and HN NA-respectively.
流感病毒的神经氨酸酶（NA）负责病毒的增殖和感染，促使人们努力发现和优化有效的神经氨酸酶抑制剂。本研究的主要目的是发现一种来自叶子（GCL）的新的潜在神经氨酸酶抑制剂。采用生物测定指导的分离方法获得先导化合物。采用分子对接研究预测分离化合物的结合相互作用。鉴定出具有 Log > 5.0 的 friedeline（GC1）、两种 lanastone 衍生物（3α,23-二羟基-17,14-friedolanstan-8,14,24-三烯-26-酸甲酯（GC2）和 24E-3a,9,23-三羟基-17,14-friedolanostan-14,24-二烯-26-酸甲酯（GC3））和儿茶素（GC4，Log = 1.4）。发现这四种化合物对 NA 和 HN 的抑制活性如下：GC4 > GC2 > GC3 > GC1。所有化合物对 NA 的抑制活性均高于 HN NA。从分子对接结果来看，GC4 与 Arg118、Arg371、Arg292、Glu276 和 Trp178 残基有利地对接并相互作用，而 GC2 与 Arg118、Arg371、Arg292、Ile222、Arg224 和 Ser246 相互作用。GC3 仅与 Tyr406 相互作用。GC4 具有强大的 NA 抑制作用，结合自由能为-12 kcal/mol。在酶抑制研究中，GC4 对 NA 和 HN NA 的 IC 分别为 60.3 μM 和 91.0 μM，显示出最高的活性。
