The structure of mezerein, a major toxic principle of daphne mezereum L.

Ronlán, Alvin; Wickberg, Börje

doi:10.1016/s0040-4039(00)89459-9

Cited by 51 publications

(21 citation statements)

References 4 publications

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“…Daphnetoxin was identified by IR, UV, NMR ( 1 H and 13 C) and mass spectra, melting point and specific optical rotation ([a] D 25 : + 368; c 0.08; CHCl 3 ). All data were in accord with those described in the literature (8), (11).…”

Section: Isolation and Identification Of Daphnetoxinmentioning

confidence: 55%

“…Compounds extracted from Daphne species are known to exhibit toxic effects evaluated by toxicity tests using goldfish (2), (11), (16) and by irritant effects in rat skin (8), (14). However, some of them may also exhibit antileukemic activity as shown by tests performed according to the standard protocols Fig.…”

Section: Discussionmentioning

confidence: 99%

“…1). Although mezerein and daphnetoxin share similarities on their toxicity (8), the antileukemic properties of mezerein are not shared by daphnetoxin (9). The molecular mechanisms for these differences on the biological activities remain to be determined.…”

Section: Introductionmentioning

confidence: 99%

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Differential Activation by Daphnetoxin and Mezerein of PKC-Isotypes α, βI, δ and ζ

Fresco¹,

Pinto²,

Portugal³

et al. 2001

Planta med

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Daphnetoxin, a mezerein derivative, was isolated from the stem bark of Daphne gnidium. Mezerein is a PKC activator that exhibits antileukemic properties. However, daphnetoxin and its analogue 12-hydroxydaphnetoxin were described as being devoid of this effect. In the present study daphnetoxin and mezerein were compared as PKC activators on classical (alpha and beta I), novel (delta) and atypical (zeta) isoforms, using an alternative in vivo yeast phenotypic assay. The aim was to clarify if daphnetoxin is a PKC activator and if the differences between the antiproliferative effect of mezerein and of its analogue daphnetoxin may be ascribed to differences on their potency or selectivity as PKC activators. Yeast samples expressing each of the mammalian PKC isoforms tested were incubated with daphnetoxin or mezerein. Growth inhibition caused by these drugs was assumed to be due to PKC activation since it did not occur when expression was not induced. Mezerein inhibited the growth of yeast expressing PKC alpha (IC(50) = 1190 +/- 237 nM; n = 20), PKC beta I (IC(50) = 908 +/- 46 nM; n = 20), and PKC delta (IC(50) = 141 +/- 25 nM; n = 20) but not of yeast expressing PKC zeta. Daphnetoxin also inhibited the growth of yeast expressing isoforms alpha, beta I and delta, being more potent than mezerein on PKC alpha (IC(50) = 536 +/- 183 nM; n = 20; P < 0.05), as potent as mezerein on PKC beta I (IC(50) = 902 +/- 129 nM; n = 20) and less potent than mezerein upon PKC delta (IC(50) = 3370 +/- 492 nM; n = 20; P < 0.05). These results show that daphnetoxin is a potent PKC activator but with a selectivity different from that of mezerein. It is suggested that the lack of antileukemic and antiproliferative effects of daphnetoxin may be due to its lower potency to activate PKC delta.

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Section: Isolation and Identification Of Daphnetoxinmentioning

confidence: 55%

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Differential Activation by Daphnetoxin and Mezerein of PKC-Isotypes α, βI, δ and ζ

Fresco¹,

Pinto²,

Portugal³

et al. 2001

Planta med

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show abstract

“…The medicinal use of mezereon caused several fatalities and is now completely obsolete [15]. Daphnetoxin was later isolated also from other Daphne species [16][17][18] . The structure of daphnetoxin was secured by an X-ray analysis of the 5,20-bisbromoacetate [15].…”

Section: Daphnetoxin and Analoguesmentioning

confidence: 99%

“…This compound is also a very potent neurotrophic agent [44], and show nM-level anticancer activity in human leukaemia cells [45]. Mezerein (6) is the archetypal 12-acyloxyderivative of daphnetoxin, and was first isolated from the bark and the seeds of D. mezereum [15,17,[46][47][48], a plant firmly enshrined in the Greek and Roman medicinal tradition as a treatment of various cancerous conditions [49]. It was also isolated as the poisonous principle of Lasiosiphon burchellii (Thymelaeaceae), a South African plant involved in livestock poisoning [16].…”

Section: Daphnetoxin and Analoguesmentioning

confidence: 99%