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

被引：5

作者：

Fois, Benedetta ^{[1
]}

Corona, Angela ^{[1
]}

Tramontano, Enzo ^{[1
,2
]}

Distinto, Simona ^{[1
]}

Maccioni, Elias ^{[1
]}

Meleddu, Rita ^{[1
]}

Caboni, Pierluigi ^{[1
]}

Floris, Costantino ^{[3
]}

Cottiglia, Filippo ^{[1
]}

机构：

[1] Univ Cagliari, Cittadella Univ Monserrato, Dept Life & Environm Sci, I-09042 Monserrato, Italy

[2] CNR, Ist Ric Genet & Biomed, Monserrato, Italy

[3] Univ Cagliari, Dept Chem & Geol Sci, Monserrato, Italy

来源：

JOURNAL OF ENZYME INHIBITION AND MEDICINAL CHEMISTRY | 2021年 / 36卷 / 01期

关键词：

HIV; RNase H; reverse transcriptase; Teucrium flavum; neo-clerodane diterpenes; flavonoids; DUAL INHIBITORS; FORCE-FIELD; INTEGRASE; RESISTANT; IDENTIFICATION; CONSTITUENTS; DESIGN;

D O I：

10.1080/14756366.2021.1887170

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

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 mu M. 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.

引用

页码：749 / 757

页数：9

共 12 条

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