A Dimeric Lactone from <i>Ardisia japonica</i> with Inhibitory Activity for HIV-1 and HIV-2 Ribonuclease H

Dat, Nguyen Tien; Bae, KiHwan; Wamiru, Antony; McMahon, James B.; Grice, Stuart F. J. Le; Bona, Marion K.; Beutler, John A.; Kim, Young Ho

doi:10.1021/np060359m

Cited by 36 publications

(26 citation statements)

References 21 publications

(30 reference statements)

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“…Such drugs would likely be active against all current drug-resistant viral strains, because the RNase H active site is located at the opposite end of the enzyme from the polymerase domain (ϳ50 Å away) that is currently targeted by nucleoside and nonnucleoside RT inhibitors (79). Several compounds have been found in recent years to effectively inhibit the RNase H activity of HIV-1 RT, including ␣,␥-diketo acids and derivatives (27,77,78,91), pyrimidinol carboxylic acids (43,47), hydroxytropolones (including ␤-thujaplicinol) (6,12,15,21,34), dimeric lactones (19), 1,3,4,5-tetragalloylapiitol (86), phenolic glycosides (10), vinylogous ureas (16,94), N-hydroxyimides (33,44), 2-hydroxyisoquinoline-1,3(2H,4H)-diones (8,9), acylhydrazones (11,30,35,80), and naphthyridinones (84,95). Although these inhibitors have been studied for the ability to inhibit HIV-1 RT, little is known about their effectiveness against other retroviral RTs, such as the gammaretroviral Moloney murine leukemia virus (MoMLV) and xenotropic murine leukemia virus-related virus (XMRV) RTs.…”

mentioning

confidence: 99%

Structural and Inhibition Studies of the RNase H Function of Xenotropic Murine Leukemia Virus-Related Virus Reverse Transcriptase

Kirby

Marchand

Ong

et al. 2012

Antimicrob Agents Chemother

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Using hydroxyl-radical footprinting assays, we demonstrated that the distance between the polymerase and RNase H domains in the MoMLV and XMRV RTs is longer than that in the HIV-1 RT by ϳ3.4 Å. We identified one naphthyridinone and one hydroxyisoquinolinedione as potent inhibitors of HIV-1 and XMRV RT RNases H with 50% inhibitory concentrations ranging from ϳ0.8 to 0.02 M. Two acylhydrazones effective against HIV-1 RT RNase H were less potent against the XMRV enzyme. We also solved the crystal structure of an XMRV RNase H fragment at high resolution (1.5 Å) and determined the molecular details of the XMRV RNase H active site, thus providing a framework that would be useful for the design of antivirals that target RNase H.

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mentioning

confidence: 99%

Structural and Inhibition Studies of the RNase H Function of Xenotropic Murine Leukemia Virus-Related Virus Reverse Transcriptase

Kirby

Marchand

Ong

et al. 2012

Antimicrob Agents Chemother

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“…Compound 23 inhibited HIV-1 and HIV-2 RNase H in vitro with IC 50 values of 1.5 and 1.1 M, respectively. It is worth to note that all the other compounds isolated from the above plant that lacked the galloyl unit were inactive [48].…”

Section: Natural Products and Related Derivativesmentioning

confidence: 99%

HIV-1 RT-Associated RNase H Function Inhibitors: Recent Advances in Drug Development

Tramontano

Santo

2010

CMC

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The HIV-1 genomic RNA reverse transcription is an essential step in the virus cycle carried out by the viral-coded reverse transcriptase (RT), which has two associated functions: the RNA- and DNA-dependent DNA polymerase (RDDP and DDDP) function and the ribonuclease H (RNase H) function. The RNase H function catalyzes the selective hydrolysis of the RNA strand of the RNA:DNA heteroduplex replication intermediate. The RT associated activities are both essential for HIV-1 replication and validated targets for drug development, but only the polymerase function has been widely investigated as drug target. In fact, either nucleoside or non-nucleoside RT inhibitors currently used in therapy act on the polymerase associated activity. In this review, we describe the compounds, reported up to today, which inhibit the HIV-1 RNase H function, their chemical structures, the structure-activity relationships and the mechanism of action.

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“…Recently, Dat et al 40 isolated the dimeric lactones ardimerin (74) and ardimerin digallate (75) from the extracts of Ardisia japonica, a plant used in Oriental traditional medicine as antitussive and diuretic, as well as to stop uterine bleeding. The diolide 75…”

Section: Dimeric Lactonesmentioning

confidence: 99%

Natural occurrence, biological activities and synthesis of eight-, nine-, and eleven-membered ring lactones

Ferraz¹,

Bombonato²,

Sano³

et al. 2008

Quím. Nova

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Recebido em 17/1/08; aceito em 7/4/08; publicado na web em 30/4/08 NATURAL OCCURRENCE, BIOLOGICAL ACTIVITIES AND SYNTHESIS OF EIGHT-, NINE-, AND ELEVEN-MEMBERED RING LACTONES. The natural occurrence, biological activities and synthetic approaches to natural eight-, nine-, and elevenmembered lactones is reviewed. These medium ring lactones are grouped according to ring size, and their syntheses are discussed. The structures of some natural products early identified as medium-ring lactones were revised after total synthesis.

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A Dimeric Lactone from Ardisia japonica with Inhibitory Activity for HIV-1 and HIV-2 Ribonuclease H

Cited by 36 publications

References 21 publications

Structural and Inhibition Studies of the RNase H Function of Xenotropic Murine Leukemia Virus-Related Virus Reverse Transcriptase

Structural and Inhibition Studies of the RNase H Function of Xenotropic Murine Leukemia Virus-Related Virus Reverse Transcriptase

HIV-1 RT-Associated RNase H Function Inhibitors: Recent Advances in Drug Development

Natural occurrence, biological activities and synthesis of eight-, nine-, and eleven-membered ring lactones

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