Lycorine structure-activity relationships

Evidente, Antonio; Cicala, Maria Rosaria; Randazzo, G.; Riccio, Rodolfo; Calabrese, Giuseppe; Liso, Rosalia; Arrigoni, O.

doi:10.1016/s0031-9422(00)80145-4

Cited by 36 publications

(47 citation statements)

References 6 publications

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“…sesamin and kobusin), and alkaloids (e.g. sanguinarine, berberin, aristolochic acid, and narciclasine; Bailey, 1970;Trifunovic et al, 2003;Ono et al, 2006;Evidente et al, 1983;Gardiner et al, 2008;Na et al, 2011;Hu et al, 2012;Nakagawa et al, 2012;Hara and Kurita, 2014). Interestingly, the bioactivity of berberin and coptisin has been linked to the dioxole group as a structural analog, but without this functional group (i.e.…”

Section: Discussionmentioning

confidence: 99%

The allelochemical MDCA inhibits lignification and affects auxin homeostasis

et al. 2016

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The phenylpropanoid 3,4-(methylenedioxy)cinnamic acid (MDCA) is a plant-derived compound first extracted from roots of Asparagus officinalis and further characterized as an allelochemical. Later on, MDCA was identified as an efficient inhibitor of 4-COUMARATE-CoA LIGASE (4CL), a key enzyme of the general phenylpropanoid pathway. By blocking 4CL, MDCA affects the biosynthesis of many important metabolites, which might explain its phytotoxicity. To decipher the molecular basis of the allelochemical activity of MDCA, we evaluated the effect of this compound on Arabidopsis thaliana seedlings. Metabolic profiling revealed that MDCA is converted in planta into piperonylic acid (PA), an inhibitor of CINNAMATE-4-HYDROXYLASE (C4H), the enzyme directly upstream of 4CL. The inhibition of C4H was also reflected in the phenolic profile of MDCA-treated plants. Treatment of in vitro grown plants resulted in an inhibition of primary root growth and a proliferation of lateral and adventitious roots. These observed growth defects were not the consequence of lignin perturbation, but rather the result of disturbing auxin homeostasis. Based on DII-VENUS quantification and direct measurement of cellular auxin transport, we concluded that MDCA disturbs auxin gradients by interfering with auxin efflux. In addition, mass spectrometry was used to show that MDCA triggers auxin biosynthesis, conjugation, and catabolism. A similar shift in auxin homeostasis was found in the c4h mutant ref3-2, indicating that MDCA triggers a cross talk between the phenylpropanoid and auxin biosynthetic pathways independent from the observed auxin efflux inhibition. Altogether, our data provide, to our knowledge, a novel molecular explanation for the phytotoxic properties of MDCA.

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Section: Discussionmentioning

confidence: 99%

The allelochemical MDCA inhibits lignification and affects auxin homeostasis

et al. 2016

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“…4,49,50 1 H NMR (400 MHz, CDCl 3 ): δ 6.70 (s, H-8), 6.44 (H-12), 5.89 (s, H 2 -11), 5.56 (m, H-3), 5.50 (m, H-1), 4.14 and 3.48 (1H each, d, J = 14.0 Hz, H 2 -7), 4.13 (m, H-2), 3.32 and 2.35 (br dd, J = 8.5 and 8.5 Hz, and br q, J = 8.5 and 5.2 Hz, H 2 -5), 2.84 (d, J = 10.3 Hz, H-12c), 2.84 (dd, J = 10.3 and 2.2 Hz, H-11b) and 2.59 (1H each, m, H 2 -4). 13 C NMR (75 MHz, CDCl 3 ): δ 171.8 (Me CO ), 146.5 (C-9), 143.7 (C-10), 136.1 (C-3a), 129.3 (C-7a), 127.2 (C-12a), 117.4 (C-3), 107.3 (C-8), 104.9 (C-12), 100.9 (C-11), 72.7 (C-1), 69.4 (C-2), 61.5 (C-12c), 56.8 (C-5), 53.6 (C-7), 39.2 (C-12b), 28.5 C-4), 20.9 ( Me CO).…”

Section: Methodsmentioning

confidence: 99%

“…4,49 1 H NMR (600 MHz, CDCl 3 ): δ 6.76 (s, H-8), 6.59 (s, H-12), 5.94 (s, H 2 -11), 5.75 (s, H-1), 5.45 (s, H-3), 5.27 (s, H-2), 4.18 and 3.55 (1H each, d, J = 13.9 Hz, H 2 -7), 2.89 (d, J = 10.3 Hz, H-12c), 3.38 and 2.42 (1H each, m, H 2 -5), 2.79 (d, J = 10.3 Hz, H-12b), 2.67 (m, H 2 -4), 2.09 and 1.97 (3H, each, 2×MeCO). 13 C NMR (75 MHz, CDCl 3 ): δ 171.8 and 172.3 (2× Me CO ), 146.5 (C-3a), 146.4 (C-9), 146.2 (C-10), 129.5 (C-7a), 126.6 (C-12a), 113.9 (C-3), 107.4 (C-12), 105.1 (C-8), 101.0 (C-11), 71.0 (C-2), 69.3 (C-1), 61.3 (C-12c), 58.9 (C-7), 53.9 (C-5), 40.6 (C-12b), 28.7 (C-4) 21.3 and 20.9 (2× Me CO).…”

Section: Methodsmentioning

confidence: 99%

Lycorine, the Main Phenanthridine Amaryllidaceae Alkaloid, Exhibits Significant Antitumor Activity in Cancer Cells That Display Resistance to Proapoptotic Stimuli: An Investigation of Structure−Activity Relationship and Mechanistic Insight

et al. 2009

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Twenty-two lycorine-related compounds were investigated for in vitro anti-tumor activity using four cancer cell lines displaying different levels of resistance to pro-apoptotic stimuli and two cancer cell lines sensitive to pro-apoptotic stimuli. Lycorine and six of its congeners exhibited potency in the single-digit micromolar range, while no compound appeared more active than lycorine. Lycorine also displayed the highest potential (in vitro) therapeutic ratio, being at least 15 times more active against cancer than normal cells. Our studies also showed that lycorine exerts its in vitro anti-tumor activity through cytostatic rather than cytotoxic effects. Furthermore, lycorine provided significant therapeutic benefit in mice bearing brain grafts of the B16F10 melanoma model at non-toxic doses. Thus, the results of the current study make lycorine an excellent lead for the generation of compounds able to combat cancers, which are naturally resistant to pro-apoptotic stimuli, such as glioblastoma, melanoma, non-small-cell-lung cancers, metastatic cancers, among others.

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“…For the oxidation of lycorine C2 position, Evian et al was prepared in 1983 by Evidente et al [12] Using phosphoric acid and DCC in dry DMSO solution. Jones reagents have recently been used as oxidants, but the yield of both methods is low.…”

Section: Oxidation Of C2 Positionmentioning

confidence: 99%