title: Papain-like protease (PLpro) inhibitory effects of cinnamic amides from Tribulus terrestris fruits.
abstract: Tribulus terrestris fruits are well known for their usage in pharmaceutical preparations and food supplements. The methanol extract of T. terrestris fruits showed potent inhibition against the papain-like protease (PLpro), an essential proteolylic enzyme for protection to pathogenic virus and bacteria. Subsequent bioactivity-guided fractionation of this extract led to six cinnamic amides (1-6) and ferulic acid (7). Compound 6 emerged as new compound possessing the very rare carbinolamide motif. These compounds (1-7) were evaluated for severe acute respiratory syndrome coronavirus (SARS-CoV) PLpro inhibitory activity to identify their potencies and kinetic behavior. Compounds (1-6) displayed significant inhibitory activity with IC50 values in the range 15.8-70.1 µM. The new cinnamic amide 6 was found to be most potent inhibitor with an IC50 of 15.8 µM. In kinetic studies, all inhibitors exhibited mixed type inhibition. Furthermore, the most active PLpro inhibitors (1-6) were proven to be present in the native fruits in high quantities by HPLC chromatogram and liquid chromatography with diode array detection and electrospray ionization mass spectrometry (LC-DAD-ESI/MS).
authors.affiliation: Division of Applied Life Science (BK21 plus), IALS, Graduate School of GyeongSang National University.
authors.forename: Yeong Hun
authors.initials: YH
authors.lastname: Song
authors.forename: Dae Wook
authors.initials: DW
authors.lastname: Kim
authors.forename: Marcus John
authors.initials: MJ
authors.lastname: Curtis-Long
authors.forename: Heung Joo
authors.initials: HJ
authors.lastname: Yuk
authors.forename: Yan
authors.initials: Y
authors.lastname: Wang
authors.forename: Ningning
authors.initials: N
authors.lastname: Zhuang
authors.forename: Kon Ho
authors.initials: KH
authors.lastname: Lee
authors.forename: Kwon Seok
authors.initials: KS
authors.lastname: Jeon
authors.forename: Ki Hun
authors.initials: KH
authors.lastname: Park
mesh_terms: D000577:Amides; D002934:Cinnamates / Q000302:isolation & purification / Q000494:pharmacology* / Q000627:therapeutic use; D000086782:Coronavirus 3C Proteases; D003546:Cysteine Endopeptidases / Q000235:genetics; D015853:Cysteine Proteinase Inhibitors / Q000302:isolation & purification / Q000494:pharmacology* / Q000627:therapeutic use; D004305:Dose-Response Relationship, Drug; D004926:Escherichia coli / Q000235:genetics; D005638:Fruit / Q000737:chemistry; D006801:Humans; D020128:Inhibitory Concentration 50; D007700:Kinetics; D015394:Molecular Structure; D010936:Plant Extracts / Q000737:chemistry*; D045473:Severe acute respiratory syndrome-related coronavirus / Q000201:enzymology; D045169:Severe Acute Respiratory Syndrome / Q000188:drug therapy / Q000821:virology; D013329:Structure-Activity Relationship; D032444:Tribulus / Q000737:chemistry*; D014764:Viral Proteins / Q000037:antagonists & inhibitors* / Q000235:genetics
chemical_list: D000577:Amides; D002934:Cinnamates; D015853:Cysteine Proteinase Inhibitors; D010936:Plant Extracts; D014764:Viral Proteins; D003546:Cysteine Endopeptidases; D000086782:Coronavirus 3C Proteases