Flavonoids and Acid-Hydrolysis derivatives of -Clerodane diterpenes from subsp. as inhibitors of the HIV-1 reverse transcriptase-associated RNase H function.

Bioassay-guided fractionation of the ethyl acetate extract from subsp. , endowed with inhibitory activity towards the HIV-1 reverse transcriptase-associated RNase H function, led to the isolation of salvigenin (), cirsimaritin () and cirsiliol () along with the -clerodanes teuflavin () and teuflavoside (). Acid hydrolysis of the inactive teuflavoside provided three undescribed -clerodanes, flavuglaucins A-C () and one known -clerodane (). Among all -clerodanes, flavuglaucin B showed the highest inhibitory activity towards RNase H function with a IC value of 9.1 μM. 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. -clerodanes represent a valid scaffold for the development of a new class of HIV-1 RNase H inhibitors.