Withanolide-Type Steroids from Physalis nicandroides Inhibit HIV Transcription.

The aim of the present study is to report the isolation, structural elucidation, and antiviral evaluation of four new withanolide-type steroids, named nicansteroidins A-D (1-4), together with nine related known compounds (5-13) isolated from the aerial parts of Physalis nicandroides. Their structures were established based on an extensive spectroscopic analysis, including 1D and 2D NMR techniques. Outstandingly, nicansteroidins A and B possess an unusual side chain with an exocyclic double bond on the δ-lactone system, whereas nicansteroidins C and D have an uncommon cycloperoxide functionality in ring A as distinct structural motifs. Their biological evaluation as inhibitors of human immunodeficiency virus type 1 replication revealed that two compounds from this series, 7 and 13, displayed strong inhibition of HIV-1 replication with IC50 values lower than 2 µM. Moreover, cellular mechanism experiments showed that the main target of these compounds in the HIV replication cycle is viral transcription. This study is the first report of withanolide-type steroids as HIV inhibitors and provides insight into their potential as candidates for further preclinical studies.

Effects of phenylpropanoids on human organic anion transporters hOAT1 and hOAT3.

Human organic anion transporters hOAT1/SLC22A6 and hOAT3/SLC22A8 are highly expressed on the basolateral membrane of renal proximal tubules and mediate tubular uptake of anionic drugs from blood. They play an important role for drug disposition, and therefore close studies of their ligand recognition are important for drug therapy and development. In this study, we performed uptake experiments using HEK293 and fluorescent anion 6-carboxyfluorescein to asses the effects of phenylpropanoids on hOAT1 and hOAT3. We found that phenylpropanoids, 3-(4'-isopentenyloxyphenyl)-benzoic acid (IBA), 3-(4'-isopentenyloxy-3'-methoxyphenyl)-benzoic acid (IMBA), and 3-(4'-geranyloxy-3'-methoxy phenyl)-benzoic acid (GMBA) inhibited hOAT1 and hOAT3. The Ki values for hOAT1 were comparable to that of probenecid, a strong inhibitor of hOAT1 and hOAT3. While IBA demonstrated competitive inhibition, IMBA and GMBA showed mixed-type inhibition. After preincubation and washout, the inhibitory effects remained with IMBA and GMBA but not IBA, suggesting that the functional group at 3'-position is responsible for these differences. In conclusion, IBA, IMBA, and GMBA are inhibitors of hOAT1 and hOAT3.

Prenylated Coumarins of the Genus Citrus: An Overview of the 2006- 2016 Literature Data.

O-Prenyl coumarins (3,3-dimethylallyl, geranyl-, farnesyl- and related biosynthetic derivatives) represent a class of rarely occurring natural products. In the last two decades, such secondary metabolites have been found to possess promising and effective pharmacological properties, mainly in terms of anti-cancer and anti-inflammatory properties. To date, about 160 oxyprenylated coumarins have been extracted from plants, fungi, and bacteria. The genus Citrus has been demonstrated to be among the richest source of the title products. The aim of this comprehensive review is to make a survey of the so far reported literature citations about the main O-prenyl coumarins found in this genus from phytochemical and pharmacological point of views and for which no surveys of the in so far reported literature have been made.