Study of Marine Natural Products Including Resorcyclic Acid Lactones from <i>Humicola fuscoatra</i> That Reactivate Latent HIV-1 Expression in an in Vitro Model of Central Memory CD4+ T Cells

Mejia, Eric J.; Loveridge, Steven T.; Stepan, George; Tsai, Angela; Jones, Gregg S.; Barnes, Tiffany; White, Kimberly N.; Drašković, Marija; Tenney, Karen; Tsiang, Manuel; Geleziunas, Romas; Cihlář, Tomáš; Pagratis, Nikos; Yang, Tian; Yu, Helen; Crews, Phillip

doi:10.1021/np400889x

Cited by 24 publications

(19 citation statements)

References 29 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…These metabolites displayed UV absorption maxima at 220 and 265 nm. Examination of the NMR and physiochemical data indicated metabolites (1-3) were structurally similar to previously characterized chlorinated resorcyclic acid lactones, in accord with reports in the literature (Table 3.1, 3.2; Mejia et al, 2014;Shinonaga et al, 2009). The three metabolites isolated from this endophyte shared a core structure and structural diversity arose from differential substitutions of their 14 membered rings (1-3) (Figure 3.1).…”

Section: Metabolites Of Nectria Dacryocarpa (Nb-236-7b; Daomc 251709)supporting

confidence: 86%

“…Mejia et al, 2014,). The relative stereochemical configurations of the three secondary alcohols could not be assigned based on NOESY correlations due to the flexible structure of (3) (Mejia et al, 2014). The UV spectra showed absorption maxima at 220, 264, and 315, which agrees with reported findings (Table 3.2 data; Mejia et al, 2014).…”

Section: Metabolites Of Nectria Dacryocarpa (Nb-236-7b; Daomc 251709)supporting

confidence: 86%

“…Together, the NMR and physiochemical data support the isolation of compound (1), radicicol (Figure 3.1, Table 3.1, 3.2). Mejia et al, 2014,). The relative stereochemical configurations of the three secondary alcohols could not be assigned based on NOESY correlations due to the flexible structure of (3) (Mejia et al, 2014).…”

Section: Metabolites Of Nectria Dacryocarpa (Nb-236-7b; Daomc 251709)mentioning

confidence: 99%

“…To inhibit the Hsp90 protein, radicicol competitively binds to the ATP binding pocket (IC 50 20 nM), thereby inhibiting the ATPase activity, and cellular chaperoning ability. This inhibition results in the destabilization and degradation of oncogenic proteins, which has since prompted investigation into its tumor cell growth inhibition and apoptotic properties, and application as an anti-cancer drug (Schulte et al, 1998;Mejia et al, 2014). Its antifungal activity is attributed to the inhibition of chitin synthase in the early stages, followed by inhibition of nucleic acid and protein synthesis (Fujita et al, 1999).…”

Section: Nectria Dacryocarpa (Nb-236-7b; Daomc 251709) Metabolitesmentioning

confidence: 99%

See 3 more Smart Citations

Isolation and Characterization of Biologically Active Secondary Metabolites Produced by Foliar Endophytes of Red and Black Spruce from the Acadian Forest

Daly¹

View full text Add to dashboard Cite

The spruce budworm is the most economically important destructive insect pest affecting North American forests. Some endophytes, isolated from the Acadian forest, produce secondary metabolites, toxic to the spruce budworm in planta. The aim of this study was to investigate the biologically active extracts of endophytes of red (Picea rubens) and black spruce (P. mariana). This was hypothesized to result in the isolation of antifungal and antiinsectan metabolites with structural similarities to related pathogenic toxins. From this investigation, 13 secondary metabolites were isolated. Three macrocyclic lactones (1-3) were characterized from Nectria dacryocarpa. Five aromatic polyketides (4-8) were isolated from two unique species of Penicillium cf. glaucoalbidum belonging to the Thysanophora sect. One small amino acid derived molecule, tyrosol (9) was isolated from the endophyitc P. cf. glaucoalbidum. Four lachnellulone related compounds (10-13) were isolated from Lachnellula cf. calyciformis including two new compounds (12, 13). Most purified secondary metabolites inhibited the growth of test microorganisms in vitro, including Saccharomyces cerevisiae, Bacillus subtilis, Escherichia coli, and Microbotryum violaceum.

show abstract

Section: Metabolites Of Nectria Dacryocarpa (Nb-236-7b; Daomc 251709)supporting

confidence: 86%

Section: Metabolites Of Nectria Dacryocarpa (Nb-236-7b; Daomc 251709)supporting

confidence: 86%

Section: Metabolites Of Nectria Dacryocarpa (Nb-236-7b; Daomc 251709)mentioning

confidence: 99%

Section: Nectria Dacryocarpa (Nb-236-7b; Daomc 251709) Metabolitesmentioning

confidence: 99%

See 2 more Smart Citations

Isolation and Characterization of Biologically Active Secondary Metabolites Produced by Foliar Endophytes of Red and Black Spruce from the Acadian Forest

Daly¹

View full text Add to dashboard Cite

show abstract

“…romidepsin. Romidepsin (RMD) has been shown to be a potent inducer of HIV-1 in an in vitro T-cell model of HIV latency compared with vorinostat and other HDACis in clinical development including panobinostat [45]. Also, RMD induced HIV-1 in both resting and memory CD4+ T cells isolated from HIV-infected patients on suppressive cART [46].…”

Section: Introductionmentioning

confidence: 99%

HIV-1 Latency and Eradication: Past, Present and Future

Datta¹,

Kaminski²,

Hu³

et al. 2016

CHR

View full text Add to dashboard Cite

It is well established that antiretroviral therapy (ART), while highly effective in controlling HIV replication, cannot eliminate virus from the body. Therefore, the majority of HIV-1-infected individuals remain at risk for developing AIDS due to persistence of infected reservoir cells serving as a source of virus re-emergence. Several reservoirs containing replication competent HIV-1 have been identified, most notably CD4+ T cells. Cells of the myeloid lineage, which are the first line of defense against pathogens and participate in HIV dissemination into sanctuary organs, also serve as cellular reservoirs of HIV-1. In latently infected resting CD4+ T cells, the integrated copies of proviral DNA remain in a dormant state, yet possess the ability to produce replication competent virus after cellular activation. Studies have demonstrated that modification of chromatin structure plays a role in establishing persistence, in part suggesting that latency is, controlled epigenetically. Current efforts to eradicate HIV-1 from this cell population focus primarily on a “shock and kill” approach through cellular reactivation to trigger elimination of virus producing cells by cytolysis or host immune responses. However, studies revealed several limitations to this approach that require more investigation to assess its clinical application. Recent advances in gene editing technology prompted use of this approach for inactivating integrated proviral DNA in the genome of latently infected cells. This technology, which requires a detailed understanding of the viral genetics and robust delivery, may serve as a powerful strategy to eliminate the latent reservoir in the host leading to a sterile cure of AIDS.

show abstract

Current Status of Approaches to EradicateHIVInfection

Wolkenberg

Marrouni

Converso

et al. 2021

Burger's Medicinal Chemistry and Drug Discovery

View full text Add to dashboard Cite

Direct acting antiretroviral therapy is highly effective in suppressing viremia and preventing progression of human immunodeficiency virus ( HIV ) to acquired immunodeficiency syndrome ( AIDS ), but requires strict adherence to lifelong treatment. Upon cessation of therapy, viral rebound is observed within two to four weeks. Recently, significant effort has focused on the development of a finite drug regimen capable of providing sustained virologic response for years or decades; that is, an HIV cure. This review will provide an update on the strategies being pursued and summarize advances in the medicinal chemistry of individual targets.

show abstract

Study of Marine Natural Products Including Resorcyclic Acid Lactones from Humicola fuscoatra That Reactivate Latent HIV-1 Expression in an in Vitro Model of Central Memory CD4+ T Cells

Cited by 24 publications

References 29 publications

Isolation and Characterization of Biologically Active Secondary Metabolites Produced by Foliar Endophytes of Red and Black Spruce from the Acadian Forest

Isolation and Characterization of Biologically Active Secondary Metabolites Produced by Foliar Endophytes of Red and Black Spruce from the Acadian Forest

HIV-1 Latency and Eradication: Past, Present and Future

Current Status of Approaches to EradicateHIVInfection

Contact Info

Product

Resources

About