Identification of Flavonoids from Scutellaria barbata D. Don as Inhibitors of HIV-1 and Cathepsin L Proteases and Their Structure-Activity Relationships

Tang, Ting-Ting1; Li, Su-Mei2; Pan, Bo-Wen1; Xiao, Jun-Wei1; Pang, Yu-Xin1; Xie, Shou-Xia2; Zhou, Ying1; Yang, Jian3; Wei, Ying1

2023-05-31

10.3390/molecules28114476

MOLECULES   影响因子和分区

1420-3049

Scutellaria barbata D. Don (SB, Chinese: Ban Zhi Lian), a well-known medicinal plant used in traditional Chinese medicine, is rich in flavonoids. It possesses antitumor, anti-inflammatory, and antiviral activities. In this study, we evaluated the inhibitory activities of SB extracts and its active components against HIV-1 protease (HIV-1 PR) and SARS-CoV2 viral cathepsin L protease (Cat L PR). UPLC/HRMS was used to identify and quantify the major active flavonoids in different SB extracts, and fluorescence resonance energy transfer (FRET) assays were used to determine HIV-1 PR and Cat L PR inhibitions and identify structure-activity relationships. Molecular docking was also performed, to explore the diversification in bonding patterns of the active flavonoids upon binding to the two PRs. Three SB extracts (SBW, SB30, and SB60) and nine flavonoids inhibited HIV-1 PR with an IC50 range from 0.006 to 0.83 mg/mL. Six of the flavonoids showed 10 similar to 37.6% inhibition of Cat L PR at a concentration of 0.1 mg/mL. The results showed that the introduction of the 4'-hydroxyl and 6-hydroxyl/methoxy groups was essential in the 5,6,7-trihydroxyl and 5,7,4'-trihydroxyl flavones, respectively, to enhance their dual anti-PR activities. Hence, the 5,6,7,4'-tetrahydroxyl flavone scutellarein (HIV-1 PR, IC50 = 0.068 mg/mL; Cat L PR, IC50 = 0.43 mg/mL) may serve as a lead compound to develop more effective dual protease inhibitors. The 5,7,3',4'-tetrahydroxyl flavone luteolin also showed a potent and selective inhibition of HIV-1 PR (IC50 = 0.039 mg/mL).

Scutellaria barbata D. Don flavonoids HIV-1 protease cathepsin L protease structure-activity relationships

SCI

英语

其他

Innovation Group Project of Guizhou Province[(2021)018] ; Guizhou Provincial Science and Technology Projects[SZXK059] ; Research Center of Molecular Bioactivity from Traditional Chinese Medicine and Ethnomedicine[ZK (2023) general404] ; Youth Science and Technology Talent Growth Project of Guizhou Province[gzwkj2022-467] ; null[3411-4110000520364] ; null[(2022) 253] ; null[(2020)4Y213] ; null[ZK (2022) general480]

Biochemistry & Molecular Biology ; Chemistry

Biochemistry & Molecular Biology ; Chemistry, Multidisciplinary

WOS:001005550300001

MDPI

CHEMISTRY

Web of Science

1.Guizhou Univ Tradit Chinese Med, Coll Pharm, Guiyang 550025, Peoples R China
2.Southern Univ Sci & Technol, Jinan Univ, Shenzhen Peoples Hosp, Affiliated Hosp 1,Dept Pharmacol,Clin Med Coll 2, Shenzhen 518020, Peoples R China
3.Univ Saskatchewan, Coll Pharm & Nutr, 107 Wiggins Rd, Saskatoon, SK S7N 5E5, Canada

Tang, Ting-Ting,Li, Su-Mei,Pan, Bo-Wen,et al. Identification of Flavonoids from Scutellaria barbata D. Don as Inhibitors of HIV-1 and Cathepsin L Proteases and Their Structure-Activity Relationships[J]. MOLECULES,2023,28(11).

Tang, Ting-Ting.,Li, Su-Mei.,Pan, Bo-Wen.,Xiao, Jun-Wei.,Pang, Yu-Xin.,...&Wei, Ying.(2023).Identification of Flavonoids from Scutellaria barbata D. Don as Inhibitors of HIV-1 and Cathepsin L Proteases and Their Structure-Activity Relationships.MOLECULES,28(11).

Tang, Ting-Ting,et al."Identification of Flavonoids from Scutellaria barbata D. Don as Inhibitors of HIV-1 and Cathepsin L Proteases and Their Structure-Activity Relationships".MOLECULES 28.11(2023).