Many naphthoquinone derivatives have been

Many naphthoquinone derivatives have been previously obtained from fungi in the genus Fusarium isolated from various sources, F. oxysporum from the root of citrus (Nagia and El-Mohamedy, 2007), Fusarium sp. (No. b77) from the mangrove plant (Shao et al., 2010), F. solani and F. oxysporum from fibrous roots of citrus tree (Baker et al., 1990) and F. culmorum from the wheat (Shibata et al., 1968). However, there has been only one report on the isolation of naphthoquinones from the soil fungus F. verticillioides (Boonyapranai et al., 2008). Thus, this is the second report of the naphthoquinone derivatives from soil fungus Fusarium sp.
Experimental
Acknowledgments K. Trisuwan thanks the Bioresources Research Network, National Center for Genetic Engineering and Biotechnology for a research grant (Grant No. BRN 001 G-55). V. Rukachaisirikul thanks the Thailand Research Fund for the TRF Senior Research Scholar (Grant No. RTA5480002). The Department of Chemistry, Faculty of Science, Chiang Mai University is gratefully acknowledged for partial support.
Introduction Clausena is an abundant source of secondary metabolites, especially carbazole alkaloids (Maneerat et al., 2011, 2012, 2013; Songsiang et al., 2011, 2012; Thongthoom et al., 2010), coumarins (Maneerat et al., 2012; Songsiang et al., 2011, 2012; Thongthoom et al., 2010) and amide derivitives (Riemer et al., 1997; Wang et al., 2013). Many of the isolated compounds have a wide range of pharmacological activities including anticancer (Maneerat et al., 2012, 2013; Songsiang et al., 2011; Thongthoom et al., 2010), anti-HIV (Kongkathip et al., 2005, 2010; Krahl et al., 2006), anti-malarial (Maneerat et al., 2011; Thongthoom et al., 2010) and anti-TB (Maneerat et al., 2011; Thongthoom et al., 2010). In this paper, we investigated the phytochemicals from the roots of Clausena guillauminii (Rutaceae family), which led to the isolation and characterization of two new carbazole alkaloids (1 and 2) along with sixteen known compounds (3–18). The structures of the isolated GM6001 were elucidated using spectroscopic methods especially 1D and 2D NMR spectroscopy. The structures of the known compounds were determined and confirmed by comparison of their 1H and/or 13C spectroscopic data with those reported in the literature. The cytotoxic, antimalarial and antimycobacterial activities of the isolated compounds were examined.
Experimental
Acknowledgments This work was supported by the Bioresources Research Network, National Center for Genetic Engineering and Biotechnology for research grant (Grant number BRN 001 G-56). C. Auranwiwat thanks the Science Achievement Scholarship of Thailand (SAST) for a scholarship. The Department of Chemistry, Faculty of Science, Chiang Mai University is gratefully acknowledged for partial support.
Results and discussion
Conclusion This study presents the successful preparation of new 1,2,4-trioxane-ferrocene hybrids 5–8 from ferrocene monocarboxylic acid (9), ferrocene dicarboxylic acid (12), DHA or DHA-derived precursors. Hybrids 5–8 were tested for their activity against two leukemia cells lines (the CCRF-CEM and the multidrug-resistant CEM/ADR5000 cell lines), against HCMV and against P. falciparum 3D7 parasites. All four hybrids 5–8 were more active against CCRF-CEM cells (IC50 ≤ 0.13 μM) than their parent compound DHA (IC50 of 0.48 μM). Regarding the multidrug-resistant CEM/ADR5000 cells, 1,2,4-trioxane-ferrocene hybrid 5 (IC50 of 0.53 μM) showed to be more potent than DHA (IC50 of 0.68 μM). Considering also compound 4 (IC50 of 0.25 μM), previously published by our group [71], a tendency is that hybrids with two 1,2,4-trioxane units (like compounds 6 and 8 with IC50 values of 0.07 and 0.08 μM, respectively) were at least 1.8-fold as active as the corresponding hybrids 4 and 5 with only one trioxane moiety. On the contrary, the activity of hybrids 5 (IC50 of 0.53 μM) and 4 (IC50 of 0.57 μM) against the CEM/ADR5000 cells was at least 3-fold higher than the one of compounds 6 (IC50 of 1.80 μM) and hybrids 8 (8.20 μM). Besides 1,2,4-trioxane-ferrocene-1,2,4-trioxane hybrid 8 all new hybrids showed high activity against HCMV with IC50 values lower than 0.5 μM. Thereby, all three hybrids 5–7 surpassed their parent compound DHA with its IC50 of more than 10 μM and the standard drug ganciclovir (IC50 of 2.6 μM). As in the case of their anticancer and antiviral efficacy, 1,2,4-trioxane ferrocenes are promising antimalarial compounds, and while they did not exceed their parent compounds in their antimalarial potential, their activity was still in the nanomolar range (between 7.2 nM and 30.2 nM for all hybrids).