Flavonoids and Acid-Hydrolysis derivatives ofNeo-Clerodane diterpenes fromTeucrium flavumsubsp.glaucumas inhibitors of the HIV-1 reverse transcriptase–associated RNase H function

Abstract

Bioassay-guided fractionation of the ethyl acetate extract from Teucrium flavum subsp. glaucum, endowed with inhibitory activity towards the HIV-1 reverse transcriptase-associated RNase H function, led to the isolation of salvigenin (1), cirsimaritin (2) and cirsiliol (3) along with the neo-clerodanes teuflavin (4) and teuflavoside (5). Acid hydrolysis of the inactive teuflavoside provided three undescribed neo-clerodanes, flavuglaucins A-C (7-9) and one known neo-clerodane (10). Among all neo-clerodanes, flavuglaucin B showed the highest inhibitory activity towards RNase H function with a IC 50 value of 9.1 lM. Molecular modelling and site-directed mutagenesis analysis suggested that flavuglaucin B binds into an allosteric pocket close to RNase H catalytic site. This is the first report of clerodane diterpenoids endowed with anti-reverse transcriptase activity. Neo-clerodanes represent a valid scaffold for the development of a new class of HIV-1 RNase H inhibitors.

Characterization of Essential Oils from Different Taxa Belonging to the Genus Teucrium in Sardinia Island, Italy

“…glaucum exhibited anti-inflammatory and cytotoxic activities against three tumor cell lines [ 32 ]. Recently, from the ethyl acetate extract obtained from Sardinian samples, several compounds with inhibitory activity towards the HIV-1 reverse transcriptase-associated RNase H function have been isolated [ 63 ].…”

Chemical Characterization and Anti-HIV-1 Activity Assessment of Iridoids and Flavonols from Scrophularia trifoliata

“…HIV-1 RT group M subtype B. Heterodimeric RT was expressed and purified essentially as previously [ 47 ] described. Briefly, protein was expressed in E. coli strain M15 containing the p6HRT-prot vector, induced with 1.7 mM isopropyl β- d -1-thiogalactopyranoside for 4 h. Protein purification was carried out with a BioLogic LP system (Biorad), using a combination of immobilized metal affinity and ion exchange chromatography.…”