Phytochemical Profiling,In Vitro Biological Activities,and In Silico Molecular Docking Studies of Dracaena reflexa

Dracaena reflexa, a traditionally significant medicinal plant, has not been extensively explored before for its phytochemical and biological potential. The present study was conducted to evaluate the bioactive phytochemicals and in vitro biological activities of D. reflexa, and perform in silico molecular docking validation of D. reflexa. The bioactive phytochemicals were assessed by preliminary phytochemical testing, total bioactive contents, and GC-MS analysis. For biological evaluation, the antioxidant (DPPH, ABTS, CUPRAC, and ABTS), antibacterial, thrombolytic, and enzyme inhibition (tyrosinase and cholinesterase enzymes) potential were determined. The highest level of total phenolic contents (92.72 ± 0.79 mg GAE/g extract) was found in the n-butanol fraction while the maximum total flavonoid content (110 ± 0.83 mg QE/g extract) was observed in methanolic extract. The results showed that n-butanol fraction exhibited very significant tyrosinase inhibition activity (73.46 ± 0.80) and acetylcholinesterase inhibition activity (64.06 ± 2.65%) as compared to other fractions and comparable to the standard compounds (kojic acid and galantamine). The methanolic extract was considered to have moderate butyrylcholinesterase inhibition activity (50.97 ± 063) as compared to the standard compound galantamine (53.671 ± 0.97%). The GC-MS analysis of the n-hexane fraction resulted in the tentative identification of 120 bioactive phytochemicals. Furthermore, the major compounds as identified by GC-MS were analyzed using in silico molecular docking studies to determine the binding affinity between the ligands and the enzymes (tyrosinase, acetylcholinesterase, and butyrylcholinesterase enzymes). The results of this study suggest that Dracaena reflexa has unquestionable pharmaceutical importance and it should be further explored for the isolation of secondary metabolites that can be employed for the treatment of different diseases.     

LAMOST光谱J152238.11+333136.1 P-Cygni轮廓分析

LAMOST一期巡天成功获取河外星系光谱超过150 000条,大样本光谱数据为探索奇异、稀有的天体从而完善现有的天体演化理论提供了必要的数据条件;而先进的信息技术为从海量的数据中挖掘这些珍稀样本提供了有效途径。针对采用基于DoPS的数据挖掘方法,从LAMOST DR5星系光谱数据获得的离群数据挖掘结果中,呈现出疑似P-Cygni轮廓特征的光谱J152238.11+333136.1进行了深入讨论。首先针对该光谱的基本信息、疑似P-Cygni轮廓特征以及相应的离群数据挖掘方法进行了简要表述,光谱在Hβ和[OⅢ]λ4860处呈现P-Cygni轮廓,在NeⅢλ3869和HeⅠλ5874处呈现反P-Cygni轮廓;其次,对该特征的真实性及其生成机制从以下4个角度展开讨论。(1)交叉同源观测。Sloan巡天2004年(相差11年)的同源观测,其光谱上并未呈现对应的特征,据推测可能是正在进行的演化活动或者光纤定位误差所致;(2)通过分析光谱质量、减天光残差等方法,分析P-Cygni特征是否为观测或数据处理所致。NeⅢλ3869和HeⅠλ5874处呈现反P-Cygni轮廓可信度较低;同时,通过比较目标光谱与超级天光,以及相邻光纤观测到的光谱在对应波长处的光谱特征,说明存在P-Cygni轮廓为减天光过程导致的可能性;(3)光谱子型差异。IRAS和WISE等近红外同源观测,显示其为Seyfert 2型星系,光学波段发射线强比[NⅡ]/Hα,[OⅢ]/Hβ显示其为HⅡ区,结合光学、红外测光图像特征,推测目标可能是两个星系进行并合活动;(4)从导致P-Cygni轮廓的物理机制的角度,分析了由星系并合触发外流、由恒星形成(爆发)电离气体触发的外流以及由Wolf-Rayet特征星系的超星风等原因引起的可能性。     

石杉碱甲-E2020拼合物的合成及药理研究

合成了石杉碱甲-E2020的拼合物(1),并测定了1和中间产物10和11抑制乙酰胆碱酯酶的生物活性,它们的活性均低于E2020。对E2020和其中活性最高的10的8个异构体分别进行了构象分析及与TcAChE分子对接研究,结果表明,10的各异构体中只有RRZ型与AChE的结合能比E2020高,其它异构体的结合能均远小于E2020,这可能是10的活性比E2020低的原因。对异构体RRZ还进行了与TcAChE作用方式的研究,对接结果和结合能都说明10的RRZ型异构体的活性可能比E2020高。     

4-苯基-1,3-硒唑衍生物的合成及其对蛋白酪氨酸磷酸酯酶-1B抑制活性

蛋白酪氨酸磷酸酯酶-1B(PTP1B)是抗糖尿病治疗的重要靶点,因此创制活性优良的PTP1B抑制剂具有重要意义。 本文设计并合成了11个含1,3-硒唑和1,2,4-三唑活性组块新型结构目标分子(ZLXZ1-ZLXZ11),并利用傅里叶变换红外光谱仪(FTIR)、核磁共振波谱仪(NMR)和高分辨质谱(HRMS)等对其进行了结构表征。 首先选择ZLXZ1和ZLXZ11在MOE 2015.10程序上,与PTP1B进行分子对接模拟,结果表明,在ZLXZ1分子中硒唑环上的硒原子与PTP1B中副催化位点Tyr46、Ala217、Lys120和Asp 48分别形成了π-H作用和氢键作用。 在ZLXZ11分子中硒唑上的硒原子与PTP1B中Asp181、Arg221和Asp48形成了氢键作用。 在分子对接模拟的基础上,测试了11个目标分子的抑制活性,结果表明,所有目标分子的抑制率均在87.02%以上,其中3个目标分子PTP1B抑制活性高于阳性参照物齐墩果酸,抑制活性优良,有望成为潜在的PTP1B抑制剂。     

Multiple QSAR and molecular modelling for identification of potent human adenovirus inhibitors

This study has investigated docking-based 2D- and 3D-quantitative structure-activity relationships (QSARs) for a range of 53 hydroxybenzamide analogues as anti- Human adenoviruses (HAdVs). The best 3D-QSAR (Schrodinger, LLC, NY, 2020) and 2D-QSAR models were obtained for the training set and were found to be statistically significant, with cross-validated coefficients (q²) of 0.6775 and 0.7875, and coefficients of determination (r²) of 0.8106 and 0.8122, respectively. Our in-silico docking and virtual screening studies revealed significant higher binding affinity of dataset molecule 34 (-141.444 ​kcal/mol) and hit ZINC01088642 (-114.357 ​kcal/mol) with 4PIE protein than the standard drugs. In in-silico ADME/toxicity studies, molecule 34 and proposed hit ZINC01088642 were found safe with good intestinal absorption, aqueous solubility, medium blood–brain barrier (BBB), no eye corrosion, no skin irritancy, and non-mutagenic profiles. Molecular dynamics analysis showed good stability of complex, hit ZINC01088642 with protein, 4PIE over the simulation period of 20 ns. We believe that further experimental, as well as in-vitro investigation, will shed more lights on the identification of ZINC01088642 as a potential human adenovirus agent.     

Potential bioactive compounds as SARS-CoV-2 inhibitors from extracts of the marine red alga Halymenia durvillei (Rhodophyta) – A computational study

The respiratory infection COVID-19 caused by the virus SARS CoV-2 has continued to be a major health problem worldwide and has caused more than a million mortalities. Even if the development of COVID-19 vaccines has shown much progress, efforts to find novel, natural anti-viral drugs should be pursued. Halymenia durvillei is a marine red alga widely distributed around Southeast Asia. This study aimed to develop new anti SARS CoV-2 compounds from ethanolic and ethyl acetate extracts of H. durvillei via a computational approach, focusing onthe inhibitory action against the main protease (3CL-Mpro). In this study, 37 compounds were extracted and identified by GC–MS analysis. The potentials of compounds 1–2 tetradecandiol and E,E,Z-1,3,12-nonadecatriene-5,14-diol were identified for therapeutic purposes based on our pharmacophore study, while cholest-5-En-3-Ol (3.Beta.)- had a high fitness score in molecular docking studies both in monomer and dimer state compared to the N3 inhibitor and remdesivir affinity scores. As these compounds show competitive affinity scores against the 3CL-Mpro, these natural compounds may be effective for the treatment of COVID-19 infection. The ADME and pharmacokinetic studies should also be employed to assess the ability of the natural compounds as oral drugs. These promising results have shown the potentials of H. durvillei as an alternative drug in addressing COVID-19 infection. Accordingly, further studies should explore the effectiveness of these active compounds.     

Computational Approaches to Discover Novel Natural Compounds for SARS-CoV-2 Therapeutics

Scientists all over the world are facing a challenging task of finding effective therapeutics for the coronavirus disease (COVID-19). One of the fastest ways of finding putative drug candidates is the use of computational drug discovery approaches. The purpose of the current study is to retrieve natural compounds that have obeyed to drug-like properties as potential inhibitors. Computational molecular modelling techniques were employed to discover compounds with potential SARS-CoV-2 inhibition properties. Accordingly, the InterBioScreen (IBS) database was obtained and was prepared by minimizing the compounds. To the resultant compounds, the absorption, distribution, metabolism, excretion and toxicity (ADMET) and Lipinski's Rule of Five was applied to yield drug-like compounds. The obtained compounds were subjected to molecular dynamics simulation studies to evaluate their stabilities. In the current article, we have employed the docking based virtual screening method using InterBioScreen (IBS) natural compound database yielding two compounds has potential hits. These compounds have demonstrated higher binding affinity scores than the reference compound together with good pharmacokinetic properties. Additionally, the identified hits have displayed stable interaction results inferred by molecular dynamics simulation results. Taken together, we advocate the use of two natural compounds, STOCK1N-71493 and STOCK1N-45683 as SARS-CoV-2 treatment regime.     

An efficient high-speed counter-current chromatography method for the preparative separation of sesquiterpenoids from the rhizomes of Cyperus rotundus L. combined with evaluation of the anti-inflammation activity in vitro and molecular docking

Cyperus rotundus L. has been extensively used in ancient medication for the treatment of different disorders worldwide, in which sesquiterpenes are the most representative components. In this study, sesquiterpenes were effectively purified by two-dimensional counter-current chromatography in combination with continuous injection and inner-recycling mode with a solvent system of n-hexane/ethyl acetate/methanol/water (1:0.2:1:0.2, v/v/v/v). For one-dimension separation, continuous injection mode was used with three times injection and the inner-recycling mode was adopted for the separation of two mixtures for two-dimensional separation. Finally, four sesquiterpenoids, including scariodione ( 1 ), cyperenoic acid ( 2 ), scariodione ( 3 ), and α-cyperone ( 4 ), were obtained with purities over 98%. Mass spectrometry and nuclear magnetic resonance were applied to identify their structures. The results from the anti-inflammation effect with zebrafish demonstrated that cyperenoic acid exhibited stronger anti-inflammation activity. Molecular docking results suggested that cyperenoic acid possessed lower binding energies –9.4545 kcal/mol with 1CX2 to form formed hydrogen bond interaction with ARG120. In general, all the obtained findings proved that the strong anti-inflammation capacity of cyperenoic acid can have the potential of being adopted for treating diseases resulting from inflammation.     

噻螨酮与人血清白蛋白的作用机制

用分子对接方法及紫外-可见吸收光谱、同步荧光光谱、三维荧光光谱等实验手段研究了噻螨酮(HEX)与人血清白蛋白(HSA)的相互作用及对HSA构象的影响.预测结果表明,HEX能与HSA发生相互作用,且作用位点site II比site I的打分小约4.5.实验结果表明,HEX猝灭HSA的内源荧光且作用机制为静态猝灭;HEX使HSA周围的微环境发生变化,导致蛋白质的肽链结构改变;298和291 K时HEX与HSA相互作用的结合常数(KA)和结合位点数分别为7.35×103 mol/L、0.82和1.02×104 mol/L、0.86,证实HEX仅在site II存在作用位点;HEX与Trp214的结合距离为3.01 nm,作用力主要为氢键、范德华力和疏水作用力.这些研究所获得的多种信息有助于在分子水平上理解农药对人体造成的毒性及可能的生物累积性.     

嘧啶衍生物与人血清白蛋白的相互作用

在模拟生理条件下,运用荧光光谱、激光闪光光解(LFP)和分子对接等技术研究了8种具有抗肿瘤活性的嘧啶衍生物(PDs,其中PDs A 5-FU为成药,PDs B-H为实验室自制)与人血清白蛋白(HSA)的相互作用.利用Stern-Volmer方程和激光闪光光解技术分析了PDs对HSA的荧光猝灭机制,PDs A和B为静态猝灭,PDs G和H为动态猝灭.用双倒数曲线法得出5种PDs与HSA的结合常数Ka和结合位点数n,在测定条件下5种PDs与载体结合位点数均为1,且均以弱结合力结合,通过热力学参数ΔH,ΔS和ΔG推测出PDs B,C和E与HSA之间的作用力为静电作用力和疏水作用力,PDs A和D与HSA之间的作用力是氢键和范德华力,分子对接结果与其一致.根据F9rster非辐射能量转移理论(FRET)分析了HSA和PDs之间的结合距离(r),其结果均小于4 nm,符合能量转移理论.进一步利用同步荧光、三维荧光和圆二色光谱考察了PDs与HSA结合过程中HSA空间构象的变化,结果显示,仅PDs A和C对HSA的芳香族氨基酸周围的疏水性略有增强作用.体外实验结果表明,HSA可以作为优良的载体来运输和储存PDs A~E,这为嘧啶衍生物的后续研究提供了可参考的实验数据.