Application of Mixed Linear Model in QSAR Study of Flavonoids

doi:10. 3969/j. issn. 2096-2266. 2021. 10. 002

Abstract

Abstract:

Objective： To elucidate the structure-activity relationship between flavonoids and their antioxidant activities by constructing a quantitative structure-activity relationship（QSAR） model using mixed linear model（MLM）， hence to provide the basis for the design of these lead compounds. Methods： Literature that reported the half maximal inhibitory concentration（IC50） of flavonoids against DPPH was retrieved and collected from the PubMed database， and a database was established based on their molecular structure characteristics and IC50 values. The initial QSAR model was constructed through MLM， the five-fold cross-validation method was applied to optimize the model， and finally the prediction model was obtained. Results： The antioxidant activity of flavonoid compounds was positively correlated with the numbers of ortho-phenolic-dihydroxyl in A ring（X1） and the numbers of phenolic-hydroxyls in B ring（X2）， and negatively correlated with meta-phenolic-dihydroxyl in B ring（X3）. The optimized equation was that IC50 = 137.56-65.86X1-53.92 X2+70.85X3. Conclusion： The established QSAR model by MLM could explicitly predict the antioxidant activity of flavonoids， and provide reference for the design of antioxidants.

Key words:

"> QSAR">； flavonoids">； antioxidant activity">； mixed linear model">； five-fold cross-validation

CLC Number:

R914

Lu Ang, Yuan Shimeng, Zhang Chenggui, Ai Zhiqiong, Wu Xiumei.

Application of Mixed Linear Model in QSAR Study of Flavonoids [J]. Journal of Dali University, 2021, 6(10): 6-.

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References

〔1〕 CABELLO-VERRUGIO C， SIMON F， TROLLET C， et al. Oxidative Stress in Disease and Aging： Mechanisms and Therapies 2016〔J〕. Oxid Med Cell Longev，2017，2017：4310469.

〔2〕 LEE P， CHANDEL N S， SIMON M C. Cellular Adaptation to Hypoxia through Hypoxia Inducible Factors and beyond〔J〕. Nat Rev Mol Cell Biol，2020，21（5）：268-283.

〔3〕 GUERRA-ARAIZA C， ?魣LVAREZ-MEJ?魱A A L， S?魣NCHEZ-TORRES S， et al. Effect of Natural Exogenous Antioxidants on Aging and on Neurodegenerative Diseases〔J〕. Free Radic Res，2013，47（6/7）：451-462.

〔4〕 MITRA I， SAHA A， ROY K. Development of Multiple QSAR Models for Consensus Predictions and Unified Mechanistic Interpretations of the Free-Radical Scavenging Activities of Chromone Derivatives〔J〕. J Mol Modeling，2012，18（5）：1819-1840.

〔5〕 ABDULLAH S A， JAMIL S， BASAR N， et al. Flavonoids from the Leaves and Heartwoods of Artocarpus lowii King and Their Bioactivities〔J〕. Nat Prod Res，2017，31（10）：1113-1120.

〔6〕 KIM S B， HWANG S H， SUH H W， et al. Phytochemical Analysis of Agrimonia pilosa Ledeb， Its Antioxidant Activity and Aldose Reductase Inhibitory Potential〔J〕. Int J Mol Sci，2017，18（2）：379.

〔7〕 MOLINA G A， GONZ?魣LEZ-FUENTES F， LOSKE A M， et al. Shock Wave-Assisted Extraction of Phenolic Acids and Flavonoids from Eysenhardtia Polystachya Heartwood：Ａ Novel Method and Its Comparison with Conventional Methodologies〔J〕. Ultrason Sonochem，2020，61：104809.

〔8〕 HARSA A M， HARSA T E， DIUDEA M V. QSAR and Docking Studies of Anthraquinone Derivatives by Similarity Cluster Prediction〔J〕. J Enzyme Inhib Med Chem，2016，31（3）：508-515.

〔9〕吕庆章，李小娟，牛静，等.黄酮类化合物抗氧化活性理论研究〔J〕.河南师范大学学报（自然科学版），2009，37（3）：80-84.

〔10〕赵雪巍，刘培玉，刘丹，等.黄酮类化合物的构效关系研究进展〔J〕.中草药，2015，7（21）：3264-3271.

〔11〕 SHIN H C， ROTH H R， GAO M， et al. Deep Convolutional Neural Networks for Computer-Aided Detection： CNN Architectures， Dataset Characteristics and Transfer Learning〔J〕. IEEE Trans Med Imaging，2016，35（5）：1285-1298.

〔12〕 KIM J Y， WANG Y， SONG Y H， et al. Antioxidant Activities of Phenolic Metabolites from Flemingia philippinensis Merr. et Rolfe and Their Application to DNA Damage Protection〔J〕. Molecules，2018，23（4）：816.

〔13〕 WU J F， CHEN S B， GAO J C， et al. Antioxidants and a New Dihydroisocoumarins from Polygala hongkongensis Hemsl〔J〕. Nat Prod Res，2007，21（7）：580-584.

〔14〕 BOCHOR?魣KOV?魣 H， PAULOV?魣 H， SLANINA J， et al. Main Flavonoids in the Root of Scutellaria baicalensis Cultivated in Europe and Their Comparative Antiradical Properties〔J〕. Phytother Res，2003，17（6）：640-644.

〔15〕 WU J H， HUANG C Y， TUNG Y T， et al. Online RP-HPLC-DPPH Screening Method for Detection of Radical-Scavenging Phytochemicals from Flowers of Acacia confusa〔J〕. J Agric Food Chem，2008，56（2）：328-332.

〔16〕 KO F N， CHU C C， LIN C N， et al. Isoorientin-6"-O-glucoside， a Water-Soluble Antioxidant Isolated from Gentiana arisanensis〔J〕. Biochim Biophys Acta，1998，1389（2）：81-90.

〔17〕 BOURATOUA A， KHALFALLAH A， BENSOUICI C，et al.

Chemical Composition and Antioxidant Activity of Aerial Parts of Ferula longipes Coss. ex Bonnier and Maury〔J〕. Nat Prod Res，2018，32（16）：1873-1880.

〔18〕 MAMADALIEVA N Z， HERRMANN F， EL-READI M Z， et al. Flavonoids in Scutellaria immaculata and S. ramosissima （Lamiaceae） and Their Biological Activity〔J〕. J Pharm Pharmacol，2011，63（10）：1346-1357.

〔19〕 JUNG S J， KIM D H， HONG Y H， et al. Flavonoids from the Flower of Rhododendron yedoense var. poukhanense and Their Antioxidant Activities〔J〕. Arch Pharmacal Res，2007，30（2）：146-150.

〔20〕 ZHU L， CHEN J， TAN J， et al. Flavonoids from Agrimonia pilosa Ledeb： Free Radical Scavenging and DNA Oxidative Damage Protection Activities and Analysis of Bioactivity-Structure Relationship Based on Molecular and Electronic Structures〔J〕. Molecules，2017，22（3）：195.

〔21〕 DEMIRKIRAN O， SABUDAK T， OZTURK M， et al. Antioxidant and Tyrosinase Inhibitory Activities of Flavonoids from Trifolium nigrescens subsp. petrisavi〔J〕. J Agric Food Chem，2013，61（51）：12598-12603.

〔22〕 PATEL R V， MISTRY B M， SYED R， et al. Sulfonylpiperazines Based on a Flavone as Antioxidant and Cytotoxic Agents〔J〕. Arch Pharm （Weinheim），2019，352（9）：e1900051.

〔23〕 YUAN X， WEN H， CUI Y， et al. Phenolics from Lagotis brevituba Maxim〔J〕. Nat Prod Res，2017，31（3）：362-366.

〔24〕 NASEER S， LONE S H， LONE J A， et al. LC-MS Guided Isolation， Quantification and Antioxidant Evaluation of Bioactive Principles from Epimedium elatum〔J〕. J Chromatogr B Analyt Technol Biomed Life Sci，2015，989：62-70.

〔25〕 HAWAS U W， ABOU EL-KASSEM L T， SHAHER F， et al. In vitro Inhibition of Hepatitis C virus Protease and Antioxidant by Flavonoid Glycosides from the Saudi Costal Plant Sarcocornia fruticosa〔J〕. Nat Prod Res，2019，33（23）：3364-3371.

〔26〕 LEE D Y， SHRESTHA S， SEO W D， et al. Structural and Quantitative Analysis of Antioxidant and Low-Density Lipoprotein-Antioxidant Flavonoids from the Grains of Sugary Rice〔J〕. J Med Food，2012，15（4）：399-405.

〔27〕 ZHANG L B， LV J L， CHEN H L. Japonicasins A and B， Two New Isoprenylated Flavanones from Sophora japonica〔J〕. Fitoterapia，2013，87：89-92.

〔28〕 BENMERACHE A， BENTELDJOUNE M， ALABDUL MAGID A， et al. Chemical Composition， Antioxidant and Antibacterial Activities of Tamarix balansae J. Gay Aerial Parts〔J〕. Nat Prod Res，2017，31（24）：2828-2835.

〔29〕 TADRENT W， ALABDUL MAGID A， KABOUCHE A， et al. A New Sulfonylated Flavonoid and Other Bioactive Compounds Isolated from the Aerial Parts of Cotula anthemoides L〔J〕. Nat Prod Res，2017，31（12）：1437-1445.

〔30〕 ZHU R， JIANG C， WANG X， et al. Privacy-Preserving Construction of Generalized Linear Mixed Model for Biomedical Computation〔J〕. Bioinformatics，2020，36（S1）：i128-i135.

〔31〕 LIN C Z， ZHU C C， HU M， et al. Structure-Activity Relationships of Antioxidant Activity in vitro about Flavonoids Isolated from Pyrethrum tatsienense〔J〕. J Intercult Ethnopharmacol，2014，3（3）：123-127.

〔32〕李月仕.广西茉莉花叶黄酮类化合物抗氧化活性及其构效关系和作用机理研究〔D〕.南宁：广西中医药大学，2016.

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