Phenolic phytochemical displaying SARS-CoV papain-like protease inhibition from the seeds of Psoralea corylifolia

Abstract

Severe acute respiratory syndrome coronavirus (SARS-CoV) papain-like protease (PLpro) is a key enzyme that plays an important role in SARS virus replication. The ethanol extract of the seeds of Psoralea corylifolia showed high activity against the SARS-CoV PLpro with an IC50 of value of 15 µg/ml. Due to its potency, subsequent bioactivity-guided fractionation of the ethanol extract led to six aromatic compounds (1-6), which were identified as bavachinin (1), neobavaisoflavone (2), isobavachalcone (3), 4'-O-methylbavachalcone (4), psoralidin (5) and corylifol A (6). All isolated flavonoids (1-6) inhibited PLpro in a dose-dependent manner with IC50 ranging between 4.2 and 38.4 µM. Lineweaver-Burk and Dixon plots and their secondary replots indicated that inhibitors (1-6) were mixed inhibitors of PLpro. The analysis of KI and KIS values proved that the two most promising compounds (3 and 5) had reversible mixed type I mechanisms.

Structural elucidation ofin vitrometabolites of bavachinin in rat liver microsomes by LC-ESI-MSnand chemical synthesis

“…Bavachinin (Figure 1), isolated from P. corylifolia (Chen et al, 2012), is a prenylated flavonoid. Bavachinin exhibits antiallergic, anti-inflammatory (Chen et al, 2013(Chen et al, , 2014, antiangiogenic, antitumor (Nepal et al, 2012) and antioxidant activities (Xiao et al, 2010), and inhibits severe acute respiratory syndrome coronavirus papain-like protease (Kim et al, 2014). In our study (WO2014/169800), natural bavachinin exhibited peroxisome proliferator-activated receptor g (PPAR-g) agonist activity.…”

Metabolism and disposition of corylifol A from Psoralea corylifolia: metabolite mapping, isozyme contribution, species differences and identification of efflux transporters for corylifol A-O-glucuronide in HeLa1A1 cells

“…In addition, it also exhibited cytotoxic activity against HepG2 and Hep3B hepatocellular carcinoma cell lines, with IC 50 values of 4.6 and 13.5 μg/mL, respectively (Song et al, 2013). Besides, CA possessed weak inhibitory effects on severe acute respiratory syndrome coronavirus papain-like protease (32.3 ± 3.2 μM) (Kim et al, 2013).…”

Isobavachalcone attenuates lipopolysaccharide-induced ICAM-1 expression in brain endothelial cells through blockade of toll-like receptor 4 signaling pathways

“…Isobavachalcone is a prenylated chalcone of the flavonoid family, first isolated from PCL in 1968. Isobavachalcone is known to have a wide spectrum of biological activities including anti-viral (Kim et al, 2014), antibacterial (Kuete and Sandjo, 2012), antioxidant (Haraguchi et al, 2002), antiplatelet (Jantan et al, 2010) and estrogenic (Xin et al, 2010) effects. Isobavachalcone has been shown to induce or enhance the apoptosis of cancer cells (Nishimura et al, 2007;Szliszka et al, 2012) and inhibit tumor promotion in an in vivo two-stage mouse skin carcinogenesis test (Akihisa et al, 2006).…”