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Harziphilone and Fleephilone, Two New HIV REV/RRE Binding Inhibitors Produced by Trichoderma harzianum

During the screening of the natural products for their ability to inhibit the binding of REV (regulation of virion expression) protein to [33P] labeled RRE (REV responsive element) RNA, two novel fungal metabolites, harziphilone and fleephilone, were isolated from the butanol - methanol (1:1) extrac...

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Bibliographic Details
Published in:Journal of antibiotics 1996/10/25, Vol.49(10), pp.990-997
Main Authors: QIAN-CUTRONE, JINGFANG, HUANG, STELLA, CHANG, LI-PING, PIRNIK, DOLORES M., KLOHR, STEVEN E., DALTERIO, RICHARD A., HUGILL, ROBERT, LOWE, SUSAN, ALAM, MASUD, KADOW, KATHLEEN F.
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Language:English
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Summary:During the screening of the natural products for their ability to inhibit the binding of REV (regulation of virion expression) protein to [33P] labeled RRE (REV responsive element) RNA, two novel fungal metabolites, harziphilone and fleephilone, were isolated from the butanol - methanol (1:1) extract of the fermentation broth of Trichoderma harzianum by bioassay guided fractionation. The structures of these two new compounds were established by spectroscopic methods. Harziphilone and fleephilone showed inhibitory activity against the binding of REV-protein to RRE RNA with IC50 values of 2.0μM and 7.6μM, respectively. However both compounds did not protect CEM-SS cells from acute HIV infection at concentration levels up to 200μg/ml using an XTT dye reduction assay. In addition, harziphilone demonstrated cytotoxicity at 38μM against the murine tumor cell line M-109.
ISSN:0021-8820
1881-1469
DOI:10.7164/antibiotics.49.990