Evaluation,partial characterization and purification of acetylcholine esterase enzyme and antiangiogenic activity from marine sponges

Objective:To test three marine sponges Halichondria glabrata Keller,1891;Spirastrellapachyspira(S.pachyspira)Levi,1958 and Cliona lobata Hancock,1849 for the presence of the acetylcholinesterase(AChE)in both young and developed samples from western coastal area of India.S.pachyspira methanolic extract was selected for anti/pro angiogenic activity.Methods:They were evaluated for AChE activity using Ellman’s assay based on production of yellow colored 5-thio-2-nitrobenzoate.Purification of the enzyme was planned using ammonium sulphate precipitation and characterization by sodium dodecyl sulfate polyacrylamide gel electrophoresis.Chorioallantoic membrane(ChAM)assay model was used for angiogenic/antiangiogenic testing.Results:All the three sponges showed good specific enzyme activity and S.pachyspira contained maximum specific enzyme activity.Sixty percent of ammonium sulphate precipitation of crude protein sample gave single band at 66 kDa corresponding to the true AChE.ChAM assay was performed at 62.5,125.0 and 250.0μg/mL.Dosage beyond 250μg/mL extract showed toxic response with anti angiogenic activity at all the concentrations.Conclusions:AChE activity was detected in all samples.Extract showed good anti-angiogenic response at 62.5μg/mL.Extract was highly toxic affecting microvasculature of ChAM as well as normal growth and development of the embryo at 500μg/mL.With further characterization of bioactive compounds from the extract of S.pachyspira,the compounds can be developed for anti tumor activity.

Synthesis of Some Potential Antiangiogenic 1,3-Dihydro-1,3-dioxo-2H-isoindole Derivatives

Based on the structure-activity relationships of RGD-containing peptides, a series of 1,3-dihydro-1,3-dioxo-2H-isoindole derivatives were synthesized. All of them were first reported. Their structures were confirmed by spectral data and elemental analysis. Their ability to inhibit angiogenesis were evaluated in the chick embryo chorioallantoic membrane assay at 10-5 mol/L. Compounds 5b and 5e displayed obviously antiangiogenic activity.

Synthesis and antiangiogenic activities of 5-amino-1,3-dihydro-1,3-dioxo-2H-isoindole-2-propanoic acid derivatives

Based on the structure-activity relationships and antiangiogenic mechanism of RGD-containing peptides, a series of 5-amino- 1,3-dihydro-1,3-dioxo-2H-isoindole derivatives were synthesized. The structures were characterized by ^1H NMR, MS and elementary analysis. There ability to inhibit angiogenesis were evaluated by chick embryo chorioallantoic membrane assay at 10^-5 mol/L. Compounds 7a and 7b displayed obvious antiangiogenic activity.

Synthesis and bioactivity of novel phthalimide derivatives

Novel phthalimide derivatives （4a, 4b and 6a-6e） were designed as hybrids of thalidomide and NO-ASA, and their chemical synthesis and in vitro biological activities were presented. The preliminary results showed that compared to thalidomide 4a and 4b exhibited enhanced activities against ECV304 and HepG2 cells, whereas 6e was more potent against HepG2 cells. 2007 Yi Hua Zhang. Published by Elsevier B.V. on behalf of Chinese Chemical Society. All rights reserved.

Chemical constituents from Munronia sinica and their bioactivities

Two new minor constituents,musinisins A(1)and B(2),together with five known compounds(3-7),were isolated from the aerial parts of Munronia sinica.Their structures were established by means of spectroscopic methods and the absolute stereochemistry of 1 was determined by single crystal X-ray experiment.Compound 4 showed antiangiogenic activity evaluated by a zebrafish model and apoptosis-inducing effect on A549 lung cancer cells.