Abstract
Litsea verticillata Hance (Lauraceae), a Chinese medicine used to treat swelling caused by injury or by snake bites, was the first plant identified by our National Institutes of Health (NIH)-funded International Cooperative Biodiversity Group (ICBG) project to exhibit anti-HIV activities. From this plant, we discovered a class of 8 novel litseane compounds, prototypic sesquiterpenes, all of which demonstrated anti-HIV activities. In subsequent studies, 26 additional compounds of different structural types were identified. During our continuing investigation of this plant species, we identified two new litseanes, litseaverticillols L and M, and a new sesquiterpene butenolide, litseasesquibutenolide. Litseaverticillols L and M were found to inhibit HIV-1 replication, with an IC[Formula: see text] value of 49.6[Formula: see text][Formula: see text]M. To further determine the antiviral properties of this plant, several relatively abundant isolates, including a litseane compound, two eudesmane sesquiterpenes and three lignans, were evaluated against an additional 21 viral targets. Lignans 8 and 9 were shown to be active against the Epstein-Barr Virus (EBV), with EC[Formula: see text] values of 22.0[Formula: see text][Formula: see text]M ([Formula: see text]) and 16.2[Formula: see text][Formula: see text]M ([Formula: see text]), respectively. Since many antiviral compounds have been discovered in L. verticillata, we further prepared 38 plant extracts made from the different plant parts of 9 additional Litsea species. These extracts were evaluated for their anti-HIV and cytotoxic activities, and four of the extracts, which ranged across three different species, displayed 97-100% inhibitory effects against HIV replication without showing cytotoxicity to a panel of human cell lines at a concentration of 20 μg/mL.
Highlights
Human Immunodeficiency Virus (HIV) was first established as the viral agent that causes acquired immunodeficiency syndrome (AIDS) in humans some 30 years ago (Barré-Sinoussi et al, 1983; Broder and Gallo, 1984)
Litsea verticillata (Lauraceae) was found to be one of the first anti-HIV plant leads in our efforts to discover antiviral agents from the tropical plants in the Southern Asia area (Soejarto et al, 2006)
Due to the antiviral effects of the compounds found in the plant L. verticillata, we further investigated the anti-HIV activity of 38 extracts belonging to 9 additional Litsea plant species
Summary
Human Immunodeficiency Virus (HIV) was first established as the viral agent that causes acquired immunodeficiency syndrome (AIDS) in humans some 30 years ago (Barré-Sinoussi et al, 1983; Broder and Gallo, 1984). Our previous studies on this plant have resulted in the isolation of 34 compounds including two lignans, five butenolides and 27 sesquiterpenes Among these isolates, 21 were determined as new molecules, and 20 were found to have anti-HIV activity (Hoang et al, 2002; Zhang et al.,, 2001, 2003a, 2003b, 2005). These compounds were evaluated for their anti-HIV activity. Due to the antiviral effects of the compounds found in the plant L. verticillata, we further investigated the anti-HIV activity of 38 extracts belonging to 9 additional Litsea plant species. The current paper describes the isolation, identification/structure elucidation and biological evaluation of the isolated compounds from L. verticillata as well as the biological activity evaluation of 41 Litsea plant extracts
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