Flavonoids from Pterogyne nitens Inhibit Hepatitis C Virus Entry

Hepatitis C virus (HCV) is one of the leading causes of liver diseases and transplantation worldwide. The current available therapy for HCV infection is based on interferon-α, ribavirin and the new direct-acting antivirals (DAAs), such as NS3 protease and NS5B polymerase inhibitors. However, the high costs of drug design, severe side effects and HCV resistance presented by the existing treatments demonstrate the need for developing more efficient anti-HCV agents. This study aimed to evaluate the antiviral effects of sorbifolin (1) and pedalitin (2), two flavonoids from Pterogyne nitens on the HCV replication cycle. These compounds were investigated for their anti-HCV activities using genotype 2a JFH-1 subgenomic replicons and infectious virus systems. Flavonoids 1 and 2 inhibited virus entry up to 45.0% and 78.7% respectively at non-cytotoxic concentrations. The mechanism of the flavonoid 2 block to virus entry was demonstrated to be by both the direct action on virus particles and the interference on the host cells. Alternatively, the flavonoid 1 activity was restricted to its virucidal effect. Additionally, no inhibitory effects on HCV replication and release were observed by treating cells with these flavonoids. These data are the first description of 1 and 2 possessing in vitro anti-HCV activity

Free radical scavenging activity of Pterogyne nitens Tul. (Fabaceae)

As part of our ongoing research on antioxidant agents from Brazilian flora, twenty extracts and fractions obtained from Pterogyne nitens Tulasne (Fabaceae) were screened for free radical scavenging activity by using ABTS [2,2’-azinobis(3-ethylenebenzothiazoline-6-sulfonic acid)] and DPPH (2,2-diphenyl-1-picrylhydrazyl-hydrate) radicals colorimetric assay and -carotene bleaching test. The strongest activity was found in ethyl acetate fraction from the stem barks, exhibiting IC50 values (inìg/ml) of 2.10 ± 0.1 and 10.2 ± 0.3 on ABTS•+ and DPPH•, respectively. Additionally, chromatographic fractionation of stem barks yielding myricetin, quercitrin and mirycetrin, three flavonols with remarkable antioxidant activity

Antimicrobial activity of Piper arboreum and Piper tuberculatum (Piperaceae) against opportunistic yeasts

In the scope of our ongoing research on bioactive agents from natural sources, 24 extracts and fractions obtained from Piper arboreum Aub. and Piper tuberculatum Jacq. (Piperaceae) were screenedfor antifungal activity by using broth microdilution method. The current investigation reveals that P. arboreum extracts and fractions were more effective against Candida krusei and Candida parapsilosis than Cryptococcus neoformans. The growth of Candida albicans was weakly affected by all the tested extracts and fractions. The strongest effects were observed for hexane and ethyl acetate fractions from leaves of P. arboreum, with MIC values (in ìg/ml) of 15.6 and 31.2 ìg/ml against C. krusei, respectively. Additionally, phytochemical investigation of the hexane fraction of P. arboreum leaves furnished 3 pyrrolidine amides; piperyline, 4,5-dihydropiperyline and tetrahydropiperyline, which could be responsible, at least in part for the observed antifungal activity. The most active compound, tetrahydropiperyline, displayed MIC values of 15.6 ìg/ml against C. krusei, C. parapsilosis and C. neoformans

Study of Salmonella typhimurium mutagenicity assay of (E)-piplartine by the Ames test

Phytochemical studies carried out with Piperaceae species have shown great diversity of secondary metabolites among which are several displayed considerable biological activities. The species Piper tuberculatum has been intensively investigated and a series of amides have been described. For instance, (E)-piplartine showed significant cytotoxic activity against tumor cell lines, especially human leukemia cell lines; antifungal activity against Cladosporium species; trypanocidal activity and others. Considering the popular use of P. tuberculatum and the lack of pharmacological studies regarding this plant species, the mutagenic and antimutagenic effect of (E)-piplartine was evaluated by the Ames test, using the strains TA97a, TA98, TA100 and TA102 of Salmonella typhimurium. No mutagenic activity was observed for this compound.Key words: Piperaceae, Piper tuberculatum, (Z)-piplartine, mutagenic activated, Ames test

Hepatitis C virus in vitro replication is efficiently inhibited by acridone Fac4

Hepatitis C Virus (HCV) affects about 170 million people worldwide. The current treatment has a high cost and variable response rates according to the virus genotype. Acridones, a group of compounds extracted from natural sources, showed potential antiviral actions against HCV. Thus, this study aimed to evaluate the effect of a panel of 14 synthetic acridones on the HCV life cycle. The compounds were screened using an Huh7.5 cell line stably harboring the HCV genotype 2a subgenomic replicon SGR-JFH1-FEO. Cells were incubated in the presence or absence of compounds for 72 hours and cell viability and replication levels were assessed by MTT and luciferase assays, respectively. The acridone Fac4 at 5 μM inhibited approximately 90% of HCV replication with 100 % of cell viability. The effects of Fac4 on virus replication, entry and release steps were evaluated in Huh7.5 cells infected with the JFH-1 isolate of HCV (HCVcc). Fac4 inhibited approximately 70 % of JFH-1 replication, while no effect was observed on virus entry. The antiviral activity of Fac4 was also observed on the viral release, with almost 80% of inhibition. No inhibitory effect was observed against genotype 3 replication. Fac4 demonstrated 40% of intercalation into dsRNA, however did not inhibit T7 polymerase activity, as well as translation by IRES interaction. Although its mode of action is partly understood, the Fac4 presents significant inhibition of Hepatitis C virus replication and can therefore be considered as a candidate for the development of a future anti-HCV treatment

Nitensidine A, a guanidine alkaloid from Pterogyne nitens, induces osteoclastic cell death

Nitensidine A is a guanidine alkaloid isolated from Pterogyne nitens, a common plant in South America. To gain insight into the biological activity of P. nitens-produced compounds, we examined herein their biological effects on osteoclasts, multinucleated giant cells that regulate bone metabolism by resorbing bone. Among four guanidine alkaloids (i.e., galegine, nitensidine A, pterogynidine, and pterogynine), nitensidine A and pterogynine exhibited anti-osteoclastic effects at 10 μM by reducing the number of osteoclasts on the culture plate whereas galegine and pterogynidine did not. The anti-osteoclastic activities of nitensidine A and pterogynine were exerted in a concentration-dependent manner, whereas nitensidine A exhibited an approximate threefold stronger effect than pterogynine (IC50 values: nitensidine A, 0.93 ± 0.024 μM; pterogynine, 2.7 ± 0.40 μM). In the present study, the anti-osteoclastic effects of two synthetic nitensidine A derivatives (nitensidine AT and AU) were also examined to gain insight into the structural features of nitensidine A that exert an anti-osteoclastic effect. The anti-osteoclastic effect of nitensidine A was greatly reduced by substituting the imino nitrogen atom in nitensidine A with sulfur or oxygen. According to the differences in chemical structures and anti-osteoclastic effects of the four guanidine alkaloids and the two synthetic nitensidine A derivatives, it is suggested that the number, binding site, and polymerization degree of isoprenyl moiety in the guanidine alkaloids and the imino nitrogen atom cooperatively contribute to their anti-osteoclastic effects. © 2013 Springer Science+Business Media Dordrecht.Department of Applied Biological Chemistry, College of Bioscience and Biotechnology Chubu University, 1200 Matsumoto-cho, Kasugai, 487-8501Department of Organic Chemistry, Institute of Chemistry São Paulo State University, Araraquara, 14800-900Department of Pharmaceutical Biology, Institute of Pharmacy and Biochemistry University of Mainz, Mainz, 55128Department of Organic Chemistry, Institute of Chemistry São Paulo State University, Araraquara, 14800-90