Hinnuliquinone, a C2-symmetric dimeric non-peptide fungal metabolite inhibitor of HIV-1 protease

Singh, Sheo B.; Ondeyka, John G.; Tsipouras, Nasios; Ruby, Carolyn L.; Sardana, Vinod; Schulman, Marvin; Sánchez, María de la Paz; Peláez, Fernando; Stahlhut, Mark W.; Munshi, Sanjeev; Olsen, David B.; Lingham, Russell B.

doi:10.1016/j.bbrc.2004.08.234

Cited by 41 publications

(25 citation statements)

References 28 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…[13] Many of the endophytes have showed few biological activities of antimicrobial, antioxidant, anticancer and anti-HIV. [14,15,16] Apart from the biological properties, the reports published on endophytic antioxidant properties were very few.…”

mentioning

confidence: 99%

In vitro Antioxidant Activity and Phytochemical Screening of Endophytic Extracts of Crotalaria pallida

Govindappa

Bharath

et al. 2011

Free Radicals and Antioxidants

View full text Add to dashboard Cite

mentioning

confidence: 99%

In vitro Antioxidant Activity and Phytochemical Screening of Endophytic Extracts of Crotalaria pallida

Govindappa

Bharath

et al. 2011

Free Radicals and Antioxidants

View full text Add to dashboard Cite

“…Hinnuliquinone (191) inhibited both a WT HIV-1 protease, K i = 0.97 µM, and a clinically-resistant strain, A44, which contained a V82T mutation, with a K i = 1.25 µM. An X-ray crystallographic analysis of a hinnuliquinone-protease complex revealed that the catalytic residues Asp25 and Asp25' interacted almost symmetrically with the adjacent keto and hydroxy groups of the dihydroxy-quinone ring while the other side of the quinone ring faced the flap, engaging in H-bond interactions with the backbone amides of Ile-50 and Ile-50' [496].…”

Section: Hiv Protease Inhibitors (Hiv Pis)mentioning

confidence: 99%

“…An interesting HIV-1 protease-inhibiting natural product reported in 2004 is the C2-symmetric bis-indolyl quinone, hinnuliquinone (191), which was isolated from fungal metabolites using a bioassay-guided isolation procedure [496]. Hinnuliquinone (191) inhibited both a WT HIV-1 protease, K i = 0.97 µM, and a clinically-resistant strain, A44, which contained a V82T mutation, with a K i = 1.25 µM.…”

Section: Hiv Protease Inhibitors (Hiv Pis)mentioning

confidence: 99%

Developments in Antiviral Drug Design, Discovery and Development in 2004

Meanwell

Belema²,

Carini³

et al. 2005

CDTID

View full text Add to dashboard Cite

This article summarizes key aspects of progress made during 2004 toward the design, discovery and development of antiviral agents for clinical use. Important developments in the identification, characterization and clinical utility of inhibitors of human immunodeficiency virus; the hepatitis viruses, hepatitis B, hepatitis C; the herpes family of viruses, herpes simplex viruses 1 and 2, varicella zoster virus, Epstein-Barr virus and human cytomegalovirus; the respiratory viruses, influenza, respiratory syncytial virus, human metapneumovirus, picornaviruses, measles and the severe acute respiratory syndrome coronavirus; human papilloma virus; rotavirus; Ebola virus and West Nile virus, are reviewed.

show abstract

“…Further studies of the microbial flora characteristic of oak trees resulted in the isolation of a potentially valuable fungal specimen from the leaves of Quercus coccifera. This endophyte proved to be a synthesizer of hinnuliquinone ( Figure 2) Á a potent inhibitor of the HIV-1 protease (Singh et al 2004).…”

Section: Endophytic Natural Products As Drugs and Novel Drug Leadsmentioning

confidence: 99%

Endophytes: exploiting biodiversity for the improvement of natural product-based drug discovery

Staniek

Woerdenbag

Kayser

2008

Journal of Plant Interactions

132

View full text Add to dashboard Cite

Endophytes, microorganisms that colonize internal tissues of all plant species, create a huge biodiversity with yet unknown novel natural products, presumed to push forward the frontiers of drug discovery. Next to the clinically acknowledged antineoplastic agent, paclitaxel, endophyte research has yielded potential drug lead compounds with antibacterial, antiviral, antioxidant, insulin mimetic, anti-neurodegenerative and immunosuppressant properties. Furthermore, while being implicated in livestock neurotoxicosis, some endophyte-produced alkaloids have been shown to display insecticidal activity. The endophyte-host relationship is postulated to be a 'balanced antagonism'. Moreover, the plausibility of horizontal gene transfer (HGT) hypothesis is taken into account. Knowledge of the genetic background of endophytic natural product biosynthesis is discussed on the basis of loline alkaloids, ergopeptines, lolitrems and maytansinoids. The current dynamic progress in genomics will contribute to a better understanding of endophytic microbes and to further exploiting them as a source of pharmaceutically relevant compounds.

show abstract

Hinnuliquinone, a C2-symmetric dimeric non-peptide fungal metabolite inhibitor of HIV-1 protease

Cited by 41 publications

References 28 publications

In vitro Antioxidant Activity and Phytochemical Screening of Endophytic Extracts of Crotalaria pallida

In vitro Antioxidant Activity and Phytochemical Screening of Endophytic Extracts of Crotalaria pallida

Developments in Antiviral Drug Design, Discovery and Development in 2004

Endophytes: exploiting biodiversity for the improvement of natural product-based drug discovery

Contact Info

Product

Resources

About