Anti-Hepatitis C Virus Dinorditerpenes from the Roots of Flueggea virosa

Abstract

Along with four known terpenoids (1-4), eight new dinorditerpenes (5-12) were isolated and identified from the roots of Flueggea virosa. The absolute configurations of 4-6 were determined by the Mosher's method, and that of 5 was confirmed by single-crystal X-ray diffraction analysis. Using the hepatitis C virus cell culture infection system, compounds 1, 3, 11, and 12 exhibited significant anti-HCV activity with EC50 values of 5.6, 5.0, 7.5, and 6.6 μM, respectively. Compounds 11 and 12 were nontoxic toward the tested Huh7.5 cell lines.

Chemical Constituents from Flueggea virosa and the Structural Revision of Dehydrochebulic Acid Trimethyl Ester

“…The structure 4E-dehydrochebulic acid trimethyl ester was revised and its absolute configuration was determined for the first time. Comparing the present study with our prior investigation [4][5][6][7], it was found that the diversity in chemical constitutions of the roots were quite different from those of the twigs and leaves of F. virosa. Furthermore, 3β,12-dihydroxy-13-methylpodocarpa-6,8,11,13-tetraene (4) was found to be abundant in the twigs and leaves; however, the 12-O-methyl analogue of 4 was isolated as the main constituent in the roots [4].…”

“…Comparing the present study with our prior investigation [4][5][6][7], it was found that the diversity in chemical constitutions of the roots were quite different from those of the twigs and leaves of F. virosa. Furthermore, 3β,12-dihydroxy-13-methylpodocarpa-6,8,11,13-tetraene (4) was found to be abundant in the twigs and leaves; however, the 12-O-methyl analogue of 4 was isolated as the main constituent in the roots [4]. Although the 9(10→20)-abeo-ent-podocarpane skeleton had been reported from the roots of this plant [6], it was still rare in a natural source.…”

“…In previous reports, Securinega alkaloids have been widely regarded as a representative group of the genus Flueggea [3], formerly classified as Securinega genus. However, our prior studies have demonstrated that the roots of F. virosa contained a series of non-alkaloids, including ent-podocarpanes [4,5], 9(10→20)-abeo-ent-podocarpanes [6], 3,4-seco-ent-podocarpanes [7], and 3,4-seco-30-nor-friedelanes [6], some of which were endowed with anti-HCV activities and weak toxicities. Among them, 4-hydroxy-12-methoxy-13-methyl-3,4-secoent-podocarpa-6,8,11,13-tetraen-3-oic acid was found to be a brand new type anti-HCV podocarpanes [7], and 3,4-seco-30-nor-friedelanes [6], some of which were endowed with anti-HCV activities and weak toxicities.…”

Validation of the Ability of Selected Medicinal Plants to Control Bacterial Diseases as Applied by Local Herbalists in Kaya Tsolokero and Kaya Kauma of Kenya

“…Both alkaloids showed mild in vitro anti-HIV activity [28]. Four new securinega-type alkaloids, fluevirines A-D (1-4), along with ten known ones, were isolated from the twigs and leaves of Flueggea virosa [29,30]. Among them, fluevirine at (1) was a novel C, C-linked dimeric indolizidine alkaloid and showed weak antimicrobial activity against Staphylococcus aureus [31].…”

Synthesis of Novel Podocarpa-8,11,13-Triene-7- and 13-Nitriles and Evaluation of their Anti-Inflammatory and Cytotoxic Activity

“…Several natural podocarpanes with an aromatic ring C have been reported to exhibit various biological properties such as antitumoural, [1][2][3][4][5] antifungal, 6 5-lipoxygenase 7,8 and anti-hepatitis C viral (anti-HCV) 9 activities. Furthermore, different synthetic compounds related to podocarpanes with aromatic ring C have shown modulation of large-conductance calcium-activated potassium channels (BK channels), 10,11 antiplasmodial, 12 antiproliferative, 13 anti-inflammatory 14 and gastroprotective 15 activity.…”