Sea Urchin Embryo Assay Research Articles

Toxicity of four spill-treating agents on bacterial growth and sea urchin embryogenesis

The toxicity of spill-treating agents (STAs) is a topic that needs to be assessed prior to their potential application in environmental disasters. The aim of the present work was to study the effects of four commercial STAs (CytoSol, Finasol OSR 51, Agma OSD 569 and OD4000) on the growth of marine (Phaeobacter sp., Pseudomonas sp.) and terrestrial (Leuconostoc mesenteroides) bacteria, and sea urchin (Paracentrotus lividus) embryolarval development. In general, STA did not inhibit significantly the biomass production of the tested marine bacteria. Finasol OSR 51 and OD4000 clearly inhibited the growth of L. mesenteroides and an accurate description of the kinetics was provided by a proposed bivariate equation. For this species, a global parameter (EC50,τ) was defined to summarize the set of growth kinetics. Using this parameter Finasol OSR 51 was found to be less toxic (754μLL−1) than OD4000 (129μLL−1). For the sea urchin embryo assay, the ranking of toxicity as EC50 (μLL−1) was Agma OSD 569 (34.0)<CytoSol (26.3)<OD4000 (2.2)<Finasol OSR 51 (1.2).

ChemInform Abstract: Synthesis of Polyalkoxy‐3‐(4‐methoxyphenyl)coumarins with Antimitotic Activity from Plant Allylpolyalkoxybenzenes.

AbstractCoumarins, analogues of natural antimitotic compounds, are synthesized and tested in vivo in the phenotypic sea urchin embryo assay for antiproliferative antitubulin activity.

Cis-Restricted 3-Aminopyrazole Analogues of Combretastatins: Synthesis from Plant Polyalkoxybenzenes and Biological Evaluation in the Cytotoxicity and Phenotypic Sea Urchin Embryo Assays

We have synthesized a series of novel cis-restricted 4,5-polyalkoxydiaryl-3-aminopyrazole analogues of combretastatins via short synthetic sequences using building blocks isolated from dill and parsley seed extracts. The resulting compounds were tested in vivo in the phenotypic sea urchin embryo assay to reveal their antimitotic and antitubulin effects. The most potent aminopyrazole, 14a, altered embryonic cell division at 10 nM concentration, exhibiting microtubule-destabilizing properties. Compounds 12a and 14a displayed pronounced cytotoxicity in the NCI60 anticancer drug screen, with the ability to inhibit growth of multi-drug-resistant cancer cells.

Synthesis of Polyalkoxy-3-(4-Methoxyphenyl)Coumarins with Antimitotic Activity from Plant Allylpolyalkoxybenzenes

Novel polyalkoxy-3-(4-methoxyphenyl)coumarins – analogues of natural antimitotic compounds – were synthesized from plant allylpolyalkoxybenzenes and tested in vivo in the phenotypic sea urchin embryo assay for antiproliferative antitubulin activity.

Synthesis and antineoplastic properties of (1H-1,2,3-triazol-1-yl)furazans.

A method of 3-amino-4-[5-aryl(heteroaryl)-1H-1,2,3-triazol-1-yl)]furazan synthesis was optimized. Condensation of these compounds with 2,5-dimethoxytetrahydrofuran resulted in a series of previously unknown 4-[5-aryl(heteroaryl)-1H-1,2,3-triazol-1-yl)]-3-(pyrrol-1-yl)furazans. All target compounds were evaluated for both antimitotic microtubule destabilizing effect in a phenotypic sea urchin embryo assay and cytotoxicity in a panel of 60 human cancer cell lines. Pyrrolyl derivatives of triazolylfurazans were determined as antiproliferative compounds. The most potent microtubule targeting compounds 7a and 7e are of interest for further trials as antineoplastic agents.

Polyalkoxy Substituted 4H-Chromenes: Synthesis by Domino Reaction and Anticancer Activity

A series of 4H-chromenes containing various modifications in the ring B and polyalkoxy substituents in the ring E has been synthesized by Knoevenagel-Michael-hetero-Thorpe-Ziegler three-component domino reaction with the overall yield of 45-82%. The targeted molecules were evaluated in a phenotypic sea urchin embryo assay for antimitotic and microtubule destabilizing activity. The most active compounds 5{1,5} and 5{5,5} featured sesamol-derived ring B and m-methoxyphenyl or m-methoxymethylenedioxyphenyl ring E. Compounds 5{3,1}, 5{1,2}, 5{5,4}, 5{1,5}, and 5{5,5} exhibited strong cytotoxicity in the NCI60 human tumor cell line anticancer drug screen. Surprisingly, cell growth inhibition caused by these agents was more pronounced in the multidrug resistant NCI/ADR-RES cells than the parent OVCAR-8 cell line. The results suggest that polyalkoxy substited 4H-chromenes may prove to be advantageous for further design as anticancer agents.

Synthesis and comparative evaluation of 4-oxa- and 4-aza-podophyllotoxins as antiproliferative microtubule destabilizing agents

A series of novel 4-oxa-podophyllotoxin derivatives 7 featuring the intact lactone ring D and various substituents in rings B and E has been synthesized and evaluated in a phenotypic sea urchin embryo assay along with the representative 4-aza-analogs 5 for their antimitotic and microtubule destabilizing activity. The most active compounds exhibited myristicin-derived or a 3′,5′-dimethoxy substitution pattern in the ring E and a 6-methoxy moiety replacing the methylenedioxy ring A. Compounds 5xb, 5xe, 5yb, 7xa, 7xb, and 7xc showed potent antiproliferative effects in the NCI60 cytotoxicity screen. Notably, growth of the multi-drug resistant NCI/ADR-RES cells was more affected by these agents than the parent OVCAR-8 cell line. Although generally 4-oxa-podophyllotoxins were less potent than the respective 4-aza-derivatives in these assays, stability of the former series towards oxidation may prove to be of interest for the development of anticancer agents with in vivo activity.

Polyalkoxybenzenes from Plants. 5. Parsley Seed Extract in Synthesis of Azapodophyllotoxins Featuring Strong Tubulin Destabilizing Activity in the Sea Urchin Embryo and Cell Culture Assays

A series of 4-azapodophyllotoxin derivatives with modified rings B and E have been synthesized using allylpolyalkoxybenzenes from parsley seed oil. The targeted molecules were evaluated in vivo in a phenotypic sea urchin embryo assay for antimitotic and tubulin destabilizing activity. The most active compounds identified by the in vivo sea urchin embryo assay featured myristicin-derived ring E. These molecules were determined to be more potent than podophyllotoxin. Cytotoxic effects of selected molecules were further confirmed and evaluated by conventional assays with A549 and Jurkat human leukemic T-cell lines including cell growth inhibition, cell cycle arrest, cellular microtubule disruption, and induction of apoptosis. The ring B modification yielded 6-OMe substituted molecule as the most active compound. Finally, in Jurkat cells, compound induced caspase-dependent apoptosis mediated by the apical caspases-2 and -9 and not caspase-8, implying the involvement of the intrinsic caspase-9-dependent apoptotic pathway.

Application of plant allylpolyalkoxybenzenes in synthesis of antimitotic phenstatin analogues

Phenstatin and its derivatives with the modified ring A have been synthesized, using plant allylpolyalkoxybenzenes as a starting material. The targeted molecules were evaluated in a phenotypic sea urchin embryo assay for antiproliferative activity. It was found that phenstatin ring A modifications yielded antimitotic compounds. The most effective myristicin derivative 7d (combretastatin A-2 analogue) was determined to be ca. 10 times more potent than phenstatin, displaying antimitotic tubulin-destabilizing activity at the same concentration range as combretastatins. In contrast to combretastatins, 7d featured the steric stability with potential for further design as anticancer agent.

ChemInform Abstract: New Functionalized Aminofurazans as Potential Antimitotic Agents in the Sea Urchin Embryo Assay.

AbstractA variety of new aminofurazans is designed, synthesized and evaluated for their antimitotic activity using a sea urchin embryo assay.

New functionalized aminofurazans as potential antimitotic agents in the sea urchin embryo assay

A series of new furazan (1,2,5-oxadiazole) derivatives based on structural overlap with combretastatin have been synthesized. Targeted molecules were evaluated using the sea urchin embryo assay; several agents demonstrated 1–4 μmol dm–3 antiproliferative activity in this in vivo model.

Novel derivatives of 1,3,4-oxadiazoles are potent mitostatic agents featuring strong microtubule depolymerizing activity in the sea urchin embryo and cell culture assays

A series of novel 1,3,4-oxadiazole derivatives based on structural and electronic overlap with combretastatins have been designed and synthesized. Initially, we tested all new compounds in vivo using the phenotypic sea urchin embryo assay to yield a number of agents with anti-proliferative, anti-mitotic, and microtubule destabilizing activities. The experimental data led to identification of 1,3,4-oxadiazole derivatives with isothiazole ( 5– 8) and phenyl ( 9– 12) pharmacophores featuring activity profiles comparable to that of combretastatins, podophyllotoxin and nocodazole. Cytotoxic effects of the two lead molecules, namely 6 and 12, were further confirmed and evaluated by conventional assays with the A549 human cancer cell line including cell proliferation, cell cycle arrest at the G2/M phase, cellular microtubule distribution, and finally in vitro microtubule assembly with purified tubulin. The modeling results using 3D similarity (ROCS) and docking (FRED) correlated well with the observed activity of the molecules. Docking data suggested that the most potent molecules are likely to target the colchicine binding site.

Seasonal and spatial variation of species toxicity in Mediterranean seaweed communities: correlation to biotic and abiotic factors

The toxicity of crude extracts of 32 seaweed species from the western Mediterranean was analysed by Microtox ® assay in spring and autumn of 1996 and 1997. The species analysed rep- resented more than 76% of seaweed coverage in the 3 algal communities studied: photophilic and sciaphilic communities from the Cabrera Archipelago (Balearic Islands), and a hemisciaphilic com- munity from the Medes Archipelago (northeastern Iberian Peninsula). Most species showed seasonal variation of toxicity, which was greater in species from Cabrera than in those from Medes. Both, intra and interspecies variation of toxicity were found. Moreover, comparison of mean toxicity of these communities showed that toxicity was higher in November than in June in all cases, and that the photophilic community had both the highest number and the most toxic species. To make an ecolog- ically relevant interpretation of the toxicity detected by Microtox ® , we compared the toxicity of extracts analysed by the Microtox ® test and those analysed by the commonly used sea urchin embryo assay. In addition to seaweeds, some species of invertebrates (sponges and ascidians) were compared to ascertain whether the relationship between the 2 tests was applicable to species belonging to dif- ferent phyla. These comparisons allowed us to establish that 0.5 gamma units in Microtox ® assay is the threshold value between toxic and non-toxic species. Following a light gradient from the photo- philic to the sciaphilic communities, the seaweed species that were occasionally toxic increased while the always-toxic seaweeds decreased. Rhodophyta and Phaeophyta had a higher percentage of toxic species than Chlorophyta. Non-encrusting seaweed forms were more toxic than the encrusting ones, and in contrast to most other seaweeds, the non-encrusting calcareous species that increased cover- age from June to November simultaneously displayed a marked decrease in toxicity. We conclude that the temporal variation of toxicity observed in the seaweeds studied may be partially explained by intrinsic factors of the species (growth rates and growth shapes).

A cytotoxic principle of Tamarindus indica, di-n-butyl malate and the structure-activity relationship of its analogues.

Bioassay-guided fractionation of the methanolic extract of Tamarindus indica fruits led to the isolation of L-(-)-di-n-butyl malate which exhibited a pronounced cytotoxic activity against sea urchin embryo cells. In order to study structure-activity relationships, close-structure relatives of di-n-butyl malate were synthesized using D-(+)- and L-(-)-malic acid as starting materials, and their cytotoxic activities were examined for the sea urchin embryo assay. L-(-)-Di-n-pentyl malate was the most effective inhibitor to the development of the fertilized eggs. Significant inhibitory activity was not seen in the esters of D-(-)-isomer.

ウニはいの初期発生解析に基づく細胞分裂阻害物質の検索と化学的研究

ウニはいの初期発生解析に基づく細胞分裂阻害物質の検索と化学的研究