Altertoxins with potent anti-HIV activity from Alternaria tenuissima QUE1Se, a fungal endophyte of Quercus emoryi

Bharat P. Bashyal, Brian P. Wellensiek, Rajesh Ramakrishnan, Stanley H. Faeth, Nafees Ahmad, A. A.Leslie Gunatilaka

Research output: Contribution to journalArticle

23 Scopus citations

Abstract

Screening of a small library of natural product extracts derived from endophytic fungi of the Sonoran desert plants in a cell-based anti-HIV assay involving T-cells infected with the HIV-1 virus identified the EtOAc extract of a fermentation broth of Alternaria tenuissima QUE1Se inhabiting the stem tissue of Quercus emoryi as a promising candidate for further investigation. Bioactivity-guided fractionation of this extract led to the isolation and identification of two new metabolites, altertoxins V (1) and VI (2) together with the known compounds, altertoxins I (3), II (4), and III (5). The structures of 1 and 2 were determined by detailed spectroscopic analysis and those of 3-5 were established by comparison with reported data. When tested in our cell-based assay at concentrations insignificantly toxic to T-cells, altertoxins V (1), I (3), II (4), and III (5) completely inhibited replication of the HIV-1 virus at concentrations of 0.50, 2.20, 0.30, and 1.50 μM, respectively. Our findings suggest that the epoxyperylene structural scaffold in altertoxins may be manipulated to produce potent anti-HIV therapeutics.

Original languageEnglish (US)
Pages (from-to)6112-6116
Number of pages5
JournalBioorganic and Medicinal Chemistry
Volume22
Issue number21
DOIs
StatePublished - Nov 1 2014

Keywords

  • Alternaria tenuissima
  • Altertoxin
  • Anti-HIV activity
  • Endophytic fungus
  • V Altertoxin
  • VI

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Medicine
  • Molecular Biology
  • Pharmaceutical Science
  • Drug Discovery
  • Clinical Biochemistry
  • Organic Chemistry

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