TY - JOUR
T1 - Altertoxins with potent anti-HIV activity from Alternaria tenuissima QUE1Se, a fungal endophyte of Quercus emoryi
AU - Bashyal, Bharat P.
AU - Wellensiek, Brian P.
AU - Ramakrishnan, Rajesh
AU - Faeth, Stanley H.
AU - Ahmad, Nafees
AU - Gunatilaka, A. A.Leslie
N1 - Funding Information:
This work was supported by grants from Arizona Biomedical Research Commission (Contract No. 9014), National Cancer Institute (Grant No. R01 CA090265 ), and National Institute of General Medical Sciences (Grant No. P41 GM094060 ) and this support is gratefully acknowledged. Mr. C. Seliga and Ms. M.X. Liu are thanked for their assistance with preparation of microbial cultures and preliminary cytotoxicity evaluation of microbial extracts.
PY - 2014/11/1
Y1 - 2014/11/1
N2 - 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.
AB - 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.
KW - Alternaria tenuissima
KW - Altertoxin
KW - Anti-HIV activity
KW - Endophytic fungus
KW - V Altertoxin
KW - VI
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U2 - 10.1016/j.bmc.2014.08.039
DO - 10.1016/j.bmc.2014.08.039
M3 - Article
C2 - 25260957
AN - SCOPUS:84908433185
VL - 22
SP - 6112
EP - 6116
JO - Bioorganic and Medicinal Chemistry
JF - Bioorganic and Medicinal Chemistry
SN - 0968-0896
IS - 21
ER -