Daphnane-type diterpene esters with cytotoxic and anti-HIV-1 activities from Daphne acutiloba Rehd.

State Key Laboratory of Phytochemistry and Plant Resources in West China, Kunming Institute of Botany, Chinese Academy of Sciences, Kunming 650204, People's Republic of China.
Phytochemistry (Impact Factor: 2.55). 12/2011; 75:99-107. DOI: 10.1016/j.phytochem.2011.11.013
Source: PubMed


Seven previously unreported daphnane-type diterpene esters named acutilobins A-G, together with 12 known ones, were isolated from EtOAc extract of Daphne acutiloba Rehd. Their structures were elucidated based on the spectroscopic data. The cytotoxic and anti-HIV-1 activities of these daphnane-type diterpene esters were evaluated through bioassays. Fourteen of these isolates exhibited definite cytotoxic activities against the five human tumor cell lines HL-60, SMMC-7721, A-549, MCF-7, and SW480. Additionally, anti-HIV-1 activities were observed in 13 daphnane-type diterpene esters, among which acutilobins A-G exhibited significant anti-HIV-1 activities with EC₅₀ below 1.5 nM and SI over 10,000. Particularly, genkwanineVIII showed the strongest activity with EC₅₀ 0.17 nM and SI 187,010.

Download full-text


Available from: Sheng Zhuo Huang, May 04, 2014
  • Source
    • "This suggested that the fatty acyl group at C-13 in tigliane diterpenoid might be responsible for the moderate enhanced anti-HIV activity and cytotoxicity. Daphnane diterpenoid as 4 without a fatty acyl ortho-ester did not, however, exhibit significant anti-HIV-1 activity, while the daphnane diterpene ortho ester did as reported in previous literature [13] (Table 3). This suggests that the fatty acyl orther ester moiety is also important for the anti-HIV-1 activity in daphnane diterpenoids. "
    [Show abstract] [Hide abstract]
    ABSTRACT: Three tigliane-type diterpenoids named excoecafolins A-C and two daphnane-type diterpenoids named excoecafolins D and E, together with 13 known compounds, were isolated from the EtOAc extract of Excoecaria acerifolia Didr.. Their structures were elucidated through the analysis of the spectroscopic data. The anti-HIV-1 activity evaluation five of these compounds showed that four possessed moderate anti-HIV-1 activities with EC50 0.258, 0.036, 0.046, and 0.978 μM, SI >1,836.9, 431.1, 298.7, and >503.7, respectively. Additionally, the chemotaxonomic issue of the affinity correlation between Thymelaeceae and Euphorbiaceae is discussed based on the isolates.
    Full-text · Article · Jun 2014 · Fitoterapia
  • Source
    • "At present, different types of bioactive compounds, including phenols [4] , diterpenoids [5] , diterpene esters [6] , sesquiterpenoids [7] , lig- nans [8] , biflavonoids [9] , and coumarins and flavans [10] , have been isolated from Daphne acutiloba. Among these compounds , daphne diterpenoids, diterpene esters, sesquiterpenoids , phenols, and lignans show significant anti-HIV activities; of these the daphnane-type diterpene esters have the most potent anti-HIV-1 activities, and much higher than the other constitu- ents [4] [5] [6] [7] [8] . However, the anti-HIV activities are based on the results of primary screening in only one HIV-1 strain (HIV-1 IIIB ), and the mechanisms of action of these compounds are still unclear. "
    [Show abstract] [Hide abstract]
    ABSTRACT: Aim To evaluate the anti-HIV activity and mechanism of action of wikstroelide M, a daphnane diterpene from Daphne acutiloba Rehder (Thymelaeaceae). Methods The anti-HIV activities of wikstroelide M against different HIV strains were evaluated by cytopathic effect assay and p24 quantification assay with ELISA. The inhibitory effect of wikstroelide M on HIV reverse transcription was analyzed by real-time PCR and ELISA. The effect of wikstroelide M on HIV-1 integrase nuclear translocation was observed with a cell-based imaging assay. The effect of wikstroelide M on LEDGF/p75-IN interaction was assayed by molecular docking. Results Wikstroelide M potently inhibited different HIV-1 strains, including HIV-1IIIB, HIV-1A17, and HIV-19495, induced a cytopathic effect, with EC50 values ranging from 3.81 to 15.65 ng·mL−1. Wikstroelide M also had high inhibitory activities against HIV-2ROD and HIV-2CBL-20-induced cytopathic effects with EC50 values of 18.88 and 31.90 ng·mL−1. The inhibitory activities of wikstroelide M on the three HIV-1 strains were further confirmed by p24 quantification assay, with EC50 values ranging from 15.16 to 35.57 ng·mL−1. Wikstroelide M also potently inhibited HIV-1IIIB induced cytolysis in MT-4 cells, with an EC50 value of 9.60 ng·mL−1. The mechanistic assay showed that wikstroelide M targeted HIV-1 reverse transcriptase and nuclear translocation of integrase through disrupting the interaction between integrase and LEDGF/p75. Conclusion Wikstroelide M may be a potent HIV-1 and HIV-2 inhibitor, the mechanisms of action may include inhibition of reverse trascriptase activity and inhibition of integrase nuclear translocation through disrupting the interaction between integrase and LEDGF/p75.
    Full-text · Article · Mar 2014 · Chinese Journal of Natural Medicines
  • Source
    • "Moreover, these constituents have a variety of biological properties, such as anti-flu and antimosquito larval activities (Jayasuriya et al., 2000), inhibition of HIV-1-induced cytopathic effects (Zhang et al., 2010a,b), antiviral activities (Allard et al., 2012), cytotoxicity (Dong et al., 2011a,b; Li et al., 2011a; Tang et al., 2012c; Tempeam et al., 2005), antimicrobial activities (Tang et al., 2012a,b), and MET tyrosine kinase activities (Chen et al., 2010a,b). In addition, it was reported that daphane-type and tigliane-type diterpenoids exhibit antiviral activity (Bourjot et al., 2012; Huang et al., 2012; Vidal et al., 2012). In an ongoing chemical investigation of T. thyrsoideum (Li et al., 2011a) collected from the Yunnan province in China, thirteen new highly an, trigothysoids A–M (1–13), and three new modified daphnanes with macro-lactones, trigothysoids N–P (14–16), along with 15 known diterpenoids (17–31), were isolated. "
    [Show abstract] [Hide abstract]
    ABSTRACT: Sixteen daphnane diterpenoids, trigothysoids A-P, along with 15 known ones, were isolated from the methanol extract of the twigs and leaves of Trigonostemon thyrsoideum. Their structures were established by extensive spectroscopic techniques, including 2D NMR spectroscopy and mass spectrometry. The anti-HIV-1 activity of the compounds was also evaluated in vitro, and five compounds demonstrated potent anti-HIV-1 activity, with EC50 values of 0.015-0.001nM and TI values of 1618-17,619.
    Full-text · Article · Nov 2013 · Phytochemistry
Show more