Search

We evaluated the ability of six polyphenols isolated from the roots of Glycyrrhiza uralensis to inactivate rotaviruses, specially G5P[7] and G8P[7]. Upon finding that all polyphenols possessed anti-rotavirus activity, we evaluated whether these properties were attributable to direct inhibition of the binding of rotavirus to cells and/or to inhibition of viral replication. Using the virucidal assay, we found that all six compounds directly inhibited rotavirus binding, with activity being dependent on the type of virus. The 50% effective inhibitory concentrations (EC(50)) of the six compounds were 18.7-69.5 μM against G5P[7] and 14.7-88.1 μM against G8P[7], respectively. Five of the six compounds inhibited hemagglutination activity. Moreover, the CPE inhibition assay showed that five compounds inhibited viral replication with EC(50) values of 12.1-24.0 μM against G5P[7] and 12.0-42.0 μM against G8P[7], respectively. RT-PCR showed that the compounds suppressed viral RNA synthesis in TF-104 cells. Interestingly, the anti-rotavirus activities of four compounds were attributable to inhibition of both viral absorption and viral replication. These results suggest that compounds isolated from the roots of G. uralensis may be potent anti-rotavirus agents in vivo, acting by inhibiting both viral absorption and viral replication., (Copyright © 2010 Elsevier Ltd. All rights reserved.)

We isolated 18 polyphenols with neuraminidase inhibitory activity from methanol extracts of the roots of Glycyrrhiza uralensis. These polyphenols consisted of four chalcones (1-4), nine flavonoids (5-13), four coumarins (14-17), and one phenylbenzofuran (18). When we tested the effects of these individual compounds and analogs thereof on neuraminidase activation, we found that isoliquiritigenin (1, IC(50)=9.0 microM) and glycyrol (14, IC(50)=3.1 microM) had strong inhibitory activity. Structure-activity analysis showed that the furan rings of the polyphenols were essential for neuraminidase inhibitory activity, and that this activity was enhanced by the apioside group on the chalcone and flavanone backbone. In addition, the presence of a five-membered ring between C-4 and C-2' in coumestan was critical for neuraminidase inhibition. All neuraminidase inhibitors screened were found to be reversible noncompetitive inhibitors., (Copyright (c) 2010 Elsevier Ltd. All rights reserved.)

The organic extract of the roots of Broussonetia papyrifera showed extremely high alpha-glucosidase inhibitory activity with an IC50 of around 10 microg/mL. Due to its potency, subsequent bioactivity-guided fractionation of the chloroform extract led to 12 polyphenols, 1-12, 4 of which were identified as chalcones (1-4), another 4 as flavans (5-8), 2 as flavonols (9 and 10), and 2 others as the novel species benzofluorenones (11 and 12). Broussofluorenone A (11) and broussofluorenone B (12) emerged as new compounds possessing the very rare 5,11-dioxabenzo[b]fluoren-10-one skeleton. These compounds (1-12) were evaluated for alpha-glucosidase inhibitory activity to identify their inhibitory potencies and kinetic behavior. The most potent inhibitor, 10 (IC50=2.1 microM, Ki=2.3 microM), has an inhibitory activity slightly higher than that of the potent alpha-glucosidase inhibitor deoxynojirimycin (IC50=3.5 microM). The novel alpha-glucosidase inhibitors 11 (IC50=27.6 microM) and 12 (IC50=33.3 microM) are similar in activity to sugar-derived alpha-glucosidase inhibitors such as voglibose (IC50=23.4 microM). Interestingly, major constituents (1, 2, 6, 7, 9, and 10) of B. papyrifera displayed significant inhibitory activity with IC50 values of 5.3, 11.1, 12.0, 26.3, 3.6, and 2.1 microM, respectively. In kinetic studies, chalcones (1-4) exhibited noncompetitive inhibition characteristics, whereas the others (5-12) showed mixed behavior.

Twelve polyphenols (1-12) possessing tyrosinase inhibitory properties were isolated from the methanol (95%) extract of Morus lhou. The isolated compounds consisted of four flavanones (1-4), four flavones (5-8), and four phenylbenzofuranes (9-12). Moracin derivative 12 proved to be new a compound which was fully characterized. Compounds 1-12 were evaluated for both monophenolase and diphenolase (the two steps catalyzed by tyrosinase) inhibition to identify the structural characteristics required for mushroom tyrosinase inhibition. We observed that all parent compounds (1, 5, and 9) possessing an unsubstituted resorcinol group were highly effective inhibitors of monophenolase activity (IC(50) values of 1.3, 1.2, and 7.4 microM). The potency of the inhibitors diminished with alkyl substitution on either the aromatic ring or the hydroxyl functions. Interestingly, flavone 5 was shown to possess only monophenolase inhibitory activity, but flavanone 1 and phenylbenzofuran 9 inhibited diphenolase as well as monophenolase significantly. The inhibitory mode of these species was also dependent upon the skeleton: phenylbenzofuran 9 manifested a simple competitive inhibition mode for monophenolase and diphenolase; on the other hand flavanone 1 (monophenolase, k(3) = 0.1966 min(-1) microM(-1), k(4) = 0.0082 min(-1), and K(i)(app) = 0.0468 microM; diphenolase, k(3) = 0.0014 min(-1) microM(-1), k(4) = 0.0013 min(-1), and K(i)(app) = 0.8996 microM) and flavone 5 both showed time-dependent inhibition against monophenolase. Compound 1 operated according to the simple reversible slow binding model whereas compound 5 operated under the enzyme isomerization model.

[reaction: see text] Azophenol dyes having the permethylated cyclodextrin and/or crown moieties have been synthesized. Compound 1 provides critical information on discriminating 1-3 degrees amines with unique color changes. Addition of 1 degrees and 2 degrees amines to 1 shifts the absorbance maximum of 1 from 380 to approximately 580 and approximately 530 nm, respectively, but no change is observed with 3 degrees amines. The high selectivity of 1 is mainly due to H-bonding between the ammonium H atoms of the amine and oxygen atoms of the crown-6.

Abstract: Inhibitors of cell adhesion molecule-mediated cell adhesion might be novel therapeutic agents for the treatment of various inflammatory diseases. In this study, nine phenolic compounds were isolated from the methanol extracts of Zingiber officinale roots by bioactivity-guided fractionation. The structures of the compounds were determined by spectroscopic analysis (1H, 13C NMR and MS), to be 6-gingerol (1), 8-gingerol (2), 10-gingerol (3), 6-shogaol (4), 8-shogaol (5), 10-shogaol (6), dehydro-6-gingerdione (7), dehydro-10-gingerdione (8) and 6-paradol (9). Compounds 3, 4, 5 and 7 inhibited direct binding between sICAM-1 and LFA-1 of the THP-1 cells in a dose-dependent manner with IC50 values of 57.6, 27.1, 65.4 and 62.0μM, respectively. Compounds 4 and 7 had an inhibitory effect on direct binding between sVCAM-1 and VLA-4 of THP-1 cells. These results suggest that the phenolic compounds from Z. officinale roots are good candidates for therapeutic strategies aimed at inflammation. [Copyright &y& Elsevier]

Abstract: Quinone-methide triterpenes, celastrol (1), pristimerin (2), tingenone (3), and iguesterin (4) were isolated from Triterygium regelii and dihydrocelastrol (5) was synthesized by hydrogenation under palladium catalyst. Isolated quinone-methide triterpenes (1–4) and 5 were evaluated for SARS-CoV 3CLpro inhibitory activities and showed potent inhibitory activities with IC50 values of 10.3, 5.5, 9.9, and 2.6μM, respectively, whereas the corresponding 5 having phenol moiety was observed in low activity (IC50 =21.7μM). As a result, quinone-methide moiety in A-ring and more hydrophobic E-ring assist to exhibit potent activity. Also, all quinone-methide triterpenes 1–4 have proven to be competitive by the kinetic analysis. [Copyright &y& Elsevier]

Abstract: Natural polyphenolic compounds generally transpire to show relatively low inhibition against glycosidase including neuraminidase. In addition the inhibition modes of such compounds are rarely competitive. In this manuscript, a series of xanthone derivatives from Cudrania tricuspidata are shown to display nanomolar inhibitor activity against neuraminidase (EC 3.2.1.18) as well as competitive inhibition modes. Compound 8 bearing vicinal dihydroxy group on the A-ring displays nanomolar activity (IC50 =0.08±0.01μM), a 200-fold increase in activity relative to that of the first reported xanthone-derived neuraminidase inhibitor, mangiferin (IC50 =16.2±4.2μM). The 6,7-vicinal dihydroxy group plays a crucial role for inhibitory activity because compound 4, which has one of these hydroxyl groups prenylated was inactive (33% at 200μM), whereas other compounds (1–3 and 6–8) showed nanomolar activity (0.08–0.27μM) and competitive inhibition modes. Interestingly all inhibitors manifested enzyme isomerization inhibition against neuraminidase. The most potent inhibitor, compound 8 showed similar interaction with a transition-state analogue of neuraminic acid in active site. [Copyright &y& Elsevier]