Flavonoids and Acid-Hydrolysis derivatives of Neo-Clerodane diterpenes from Teucrium flavum subsp. glaucum as inhibitors of the HIV-1 reverse transcriptase–associated RNase H function. (1st January 2021)

• Record Type: Journal Article
• Authors: Fois, Benedetta; Corona, Angela; Tramontano, Enzo; Distinto, Simona; Maccioni, Elias; Meleddu, Rita; Caboni, Pierluigi; Floris, Costantino; Cottiglia, Filippo
• Is Part Of: Journal of enzyme inhibition and medicinal chemistry. Volume 36:Number 1(2021)
• Page Start: 749
• Page End: 757
• Publication Date: 2021-01-01
• Subjects: HIV -- RNase H -- reverse transcriptase -- Teucrium flavum -- neo-clerodane diterpenes -- flavonoids; Enzyme inhibitors -- Periodicals; Enzyme Inhibitors -- periodicals; Biochemistry -- periodicals; 572.7
• DOI: 10.1080/14756366.2021.1887170
• Languages: English
• ISSNs: 1475-6366

Abstract

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 IC50 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. Neo -clerodanes represent a valid scaffold for the development of a new class of HIV-1 RNase H inhibitors. Graphical Abstract: UF0001