title: Altertoxins with potent anti-HIV activity from Alternaria tenuissima QUE1Se, a fungal endophyte of Quercus emoryi.
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.
authors.affiliation: Southwest Center for Natural Products Research, School of Natural Resources and the Environment, College of Agriculture and Life Sciences, University of Arizona, 250 E. Valencia Road, Tucson, AZ 85706, United States.
authors.forename: Bharat P
authors.initials: BP
authors.lastname: Bashyal
authors.affiliation: Department of Immunobiology, College of Medicine, University of Arizona, Tucson, AZ 85724, United States; Biomedical Sciences Program, College of Health Sciences, Midwestern University, Glendale, AZ 85308, United States.
authors.forename: Brian P
authors.initials: BP
authors.lastname: Wellensiek
authors.affiliation: Department of Immunobiology, College of Medicine, University of Arizona, Tucson, AZ 85724, United States.
authors.forename: Rajesh
authors.initials: R
authors.lastname: Ramakrishnan
authors.affiliation: School of Life Sciences, College of Liberal Arts and Sciences, Arizona State University, Tempe, AZ 85287, United States; Department of Biology, University of North Carolina-Greensboro, Greensboro, NC 27402, United States.
authors.forename: Stanley H
authors.initials: SH
authors.lastname: Faeth
authors.affiliation: Department of Immunobiology, College of Medicine, University of Arizona, Tucson, AZ 85724, United States.
authors.forename: Nafees
authors.initials: N
authors.lastname: Ahmad
authors.affiliation: Southwest Center for Natural Products Research, School of Natural Resources and the Environment, College of Agriculture and Life Sciences, University of Arizona, 250 E. Valencia Road, Tucson, AZ 85706, United States. Electronic address: leslieg@ag.arizona.edu.
authors.forename: A A Leslie
authors.initials: AA
authors.lastname: Gunatilaka
mesh_terms: D000528:Alternaria / Q000737:chemistry* / Q000502:physiology; D019380:Anti-HIV Agents / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D001551:Benz(a)Anthracenes / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D060026:Endophytes; D015658:HIV Infections / Q000188:drug therapy; D015497:HIV-1 / Q000187:drug effects* / Q000502:physiology; D006801:Humans; D010569:Perylene / Q000031:analogs & derivatives* / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology; D029963:Quercus / Q000502:physiology; D013601:T-Lymphocytes / Q000821:virology
chemical_list: D019380:Anti-HIV Agents; D001551:Benz(a)Anthracenes; C050235:altertoxin III; C050234:altertoxin II; C050233:altertoxin I; D010569:Perylene
keywords: Alternaria tenuissima; Altertoxin V; Altertoxin VI; Anti-HIV activity; Endophytic fungus