Establishment of a Phenotypic-based Sand Dollar Fellaster zelandiae Embryo Development Assay and its Application in Defining the Structure-Activity Relationship of Discorhabdin Alkaloids
Free accessResearch articleFirst published online June, 2013
Establishment of a Phenotypic-based Sand Dollar Fellaster zelandiae Embryo Development Assay and its Application in Defining the Structure-Activity Relationship of Discorhabdin Alkaloids
An embryo development assay using the common New Zealand intertidal species Fellaster zelandiae (sand dollar) is presented. The assay was validated by comparing activity profiles of a range of discorhabdin alkaloids, natural products sourced from Latrunculia spp. sponges containing a core pyrido[2,3-h]pyrrolo[4,3,2-de]quinoline tetracyclic skeleton bound to various spiro-substituents at the C-6 position. Structural features on the discorhabdin molecule that correlated to the greatest degree of F. zelandiae embryo developmental inhibition were the presence of a spiro-dienone moiety and a C-2 bromine substituent. Based on the sand dollar embryo development assay results, a mechanism for the activity of the discorhabdin alkaloids is proposed.
(a) Environment Canada Biological Test Method: Fertilisation assay using echinoids (sea urchins, and sand dollars) (2011) EPS1/RM/27 Science and Technology Branch, Environment Canada, Ontario, Canada, pp 110; (b) Hall JA, Golding LA. (1998) Marine sand dollar (Fellaster zelandiae) short-term chronic toxicity test protocol, Appendix to: Standard Methods to Whole Effluent Toxicity Testing: Development and Application. National Institute of Water and Atmospheric Research, Wellington, New Zealand, pp 29; (c) Utkina NA, Makarchenko AE, Denisenko VA, Dmitrenok PS. (2004) Zyzzyanone A, a novel pyrrolo[3,2-f]indole alkaloid from an Australian marine sponge Zyzzya fuliginosa. Tetrahedron Letters, 45, 7491–7494; (d) Semenova MN, Kiselyov A, Semenov VV. (2006) Sea urchin embryo as a model organism for the rapid functional screening of tubulin inhibitors. BioTechniques, 40, 768–773.
2.
(a) HuJ.F., FanH.F., XiongJ., WuS-B. (2011) Discorhabdins and pyrroloiminoquinone-related alkaloids. Chemical Reviews, 111, 5465–5491;(b) Urban S, Hickford SJH, Blunt JW, Munro MHG. (2000) Bioactive marine alkaloids. Current Organic Chemistry, 4, 765–807; (c) Antunes EM, Beukes DR, Samaai T, Barrows LR, Marshall KM, Sincich C, Davies-Coleman MT. (2004) Cytotoxic pyrroloiminoquinones from four new species of South African sponges. Journal of Natural Products, 22, 1268–1276; (d) Grkovic T, Pearce AN, Munro MHG, Blunt JW, Davies-Coleman MT, Copp BR. (2010) Isolation and characterization of diastereomers of discorhabdins H and K and assignment of absolute configuration to discorhabdins D, N, Q, S, T, and U. Journal of Natural Products, 73, 1686–1693; (e) Lam CF, Grkovic T, Pearce AN, Copp BR. (2012) Investigation of the electrophilic reactivity of the cytotoxic marine alkaloid discorhabdin B. Organic & Biomolecular Chemistry, 10, 3092–3097; (f) Perry NB, Blunt JW, Munro MHG. Cytotoxic pigments from New Zealand sponges of the genus Latrunculia: discorhabdins A, B, and C. (1998) Tetrahedron, 44, 1727–1734; (g) Perry NB, Blunt JW, Munro MHG, Higa T, Sakai R. (1988) Discorhabdin D, an antitumor alkaloid from the sponges Latrunculia brevis and Prianos sp. Journal of Organic Chemistry, 53, 4127–4128; (h) Lam CFC, Giddens AC, Chand N, Webb VL, Copp BR. (2012) Semi-synthesis of bioactive fluorescent analogues of the cytotoxic marine alkaloid discorhabdin C. Tetrahedron, 68, 3187–3194.
3.
PerryN.B., BennM.H., BrennanN.J., BurgessE.J., EllisG., GallowayD.J., LorimerS.D., TangneyR.S. (1999) Antimicrobial, antiviral and cytotoxic activity of New Zealand lichens. The Lichenologist31, 627–636.
