Reactions of Alpha Methylene Lactone Tumor Inhibitors with Model Biological Nucleophiles

Kupchan, S. Morris; Fessler, Dyral C.; Eakin, M. A.; Giacobbe, Thomas J.

doi:10.1126/science.168.3929.376

Cited by 312 publications

(120 citation statements)

References 16 publications

(3 reference statements)

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“…Biological nucleophiles (e.g. amines, alcohols, sulfhydryl groups) can add to the P-carbon of the unsaturated aldehyde in a 'Michael Addition' reaction (Kupchan et al 1970). Little is known, however, regarding the interactions of enol-acetate functionalities with biological molecules.…”

Section: Toxic and Deterrent Secondary Metabolitesmentioning

confidence: 99%

Chemical defense in tropical green algae, order Caulerpales

Paul¹,

Fenical²

1986

Mar. Ecol. Prog. Ser.

181

119

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Forty marine algae of the order Caulerpales were chemically investigated. Virtually all produce toxic secondary metabolites of a unique and unprecedented class. These metabolites are generally Linear terpenoids, but unusual structural features such as aldehydes and bis-enol acetate functional groups make these compounds uruque. The conlpounds are t o n c or deterrent toward microorganisms, sea urchin larvae, and herbivous fishes, and when incorporated into diets at naturally occurring concentrations cause mortality in juvenile conch. Concentrations of bioactive metabolites were found to show httle variation in different plant parts such as blades, shpes and holdfasts. Young growlng tips and reproductive structures contained higher concentrahons than mature plant tissues on a dry weight and ash-free dry weight basis. Chemical variation, both qualitahve and quantitative, was observed in different populations of the same species. In the cases examined, algae growing in areas known to have the highest herbivory produced the greatest concentrations and varieties of secondary metabolites. Based upon these observations and pnor feeding preference data, we conclude that chemical defense IS a major factor In the sumval of marine algae within this order.

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Section: Toxic and Deterrent Secondary Metabolitesmentioning

confidence: 99%

Chemical defense in tropical green algae, order Caulerpales

Paul¹,

Fenical²

1986

Mar. Ecol. Prog. Ser.

181

119

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“…One type of binding between Jatrophone and DNA and Jatrophone-Jatrophone interactions when these molecules begin to crowd together on the DNA outer surface. These results may be important to account for the biological activity of Jatrophone besides the mechanism of the nucleophilic addition of the sulfhydryl groups [5,7].…”

Section: Resultsmentioning

confidence: 97%

“…1 \\ * To whom correspondence should be addressed at: Istituto di Chimica-Fisica, Istituto Chimico, Citt~ Universitaria, 00185 Roma, Italy [5,6]; nucleophilic addition of thiol groups on proteins to the a~-unsaturated lactone may be involved as in the case of RNA polymerase with loss of enzymatic activity [7]. Jatrophone is insoluble in water so that its pharmacological application is almost limited.…”

Section: Introductionmentioning

confidence: 99%

On the interaction between jatrophone and DNA

1981

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“…Os resultados encontrados para as lactonas (12) e (13), derivadas do 2,4-dimetil-8-oxabiciclo[3.2.1]-oct-6-en-3-ona (3), não diferiram significativamente entre si (Figuras 2 e 3). Entretanto, a posição ocupada pelo grupo metila no carbono C4 em (12) é estrategicamente importante, uma vez que sua conversão no grupo metileno pode resultar na potencialização da atividade biológica 23 . A menor porcentagem de inibição sobre o crescimento radicular em sorgo foi de 74,1%, quando se utilizou a solução 100 mg mL -1 de (12), e a maior porcentagem (90%) foi encontrada para a lactona (13), quando se utilizou a solução 250 mg mL -1 .…”

Section: Esquemaunclassified

Síntese e avaliação da atividade fitotóxica de lactonas derivadas do 2,4-dimetil-8-oxabiciclo[3.2.1]-oct-6-en-3-ona

Barbosa¹,

Maltha²,

Borges³

2002

Quím. Nova

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Recebido em 7/11/00; aceito em 25/7/01 SYNTHESIS AND PHYTOTOXIC ACTIVITY EVALUATION OF LACTONE DERIVATIVES OF 2,4-DIMETHYL-8-OXABICYCLO[3.2.1]-OCT-6-EN-3-ONE. The alkene 2,4-dimethyl-8-oxabicyclo[3.2.1]-oct-6-en-3-one (3) was converted to 1,3,10-trimethyl-8-oxabicyclo[5.3.0]-dec-3-ene-2,9-dione (7) and 1,3-dimethyl-8-oxabicyclo[5.3.0]-dec-3-ene-2,9-dione (8) with a 55% overall yield in both cases. Lactones (7) and (8) were converted in two steps to 1,3,4-trimethyl-13-methylene-6-oxatricyclo[8.3.0.0 3,7 ]-trideca-2,5,12-trione (12) (63%) and 1,3-dimethyl-13-methylene-6-oxatricycle[8.3.0.0 3,7 ]-trideca-2,5,12-trione (13) (45% from 8). The effect of lactones (7), (8), (12), (13) and the intermediates (5) and (6), at the concentration of 250 mg mL -1 , on the growth of Cucumis sativus L. and Sorghum bicolor L. was evaluated. The best results were observed for lactone (13) that caused 100% inhibition on the root growth of C. sativus and lactone (12) that inhibited 90% of the root growth for S. bicolor.

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Reactions of Alpha Methylene Lactone Tumor Inhibitors with Model Biological Nucleophiles

Cited by 312 publications

References 16 publications

Chemical defense in tropical green algae, order Caulerpales

Chemical defense in tropical green algae, order Caulerpales

On the interaction between jatrophone and DNA

Síntese e avaliação da atividade fitotóxica de lactonas derivadas do 2,4-dimetil-8-oxabiciclo[3.2.1]-oct-6-en-3-ona

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