RESUMO
A series of 'retinoid-like chalcones' and diverse derivatives relative to licochalcone A were synthesized from a new enaminone synthon. These syntheses occurred via a new aromatic annelation. These new derivatives have been tested in vitro as potential antimalarial agents. The 4-hydroxy-chalcone-like (compound 6a, derived from beta-ionone) exhibits a good and reproducible inhibitory effect on the in vitro culture of Plasmodium falciparum, with an IC 50 lower than 10 microM for inhibition of 3H-hypoxanthine uptake by parasites (respectively, 4.93 and 8.47 microM for strains K1 and Thaï).
Assuntos
Antimaláricos/síntese química , Chalcona/síntese química , Eritrócitos/parasitologia , Plasmodium falciparum/efeitos dos fármacos , Retinoides/síntese química , Animais , Antimaláricos/química , Antimaláricos/farmacologia , Chalcona/análogos & derivados , Chalcona/farmacologia , Humanos , Concentração Inibidora 50 , Malária/sangue , Malária/tratamento farmacológico , Malária/parasitologia , Parasitemia/tratamento farmacológico , Plasmodium falciparum/crescimento & desenvolvimento , Plasmodium falciparum/metabolismo , Retinoides/química , Retinoides/farmacologiaRESUMO
We have synthesized a series of 3-substituted succinimides and their in vitro antibacterial activities have been tested towards Gram-positive and Gram-negative bacteria from the ATCC collection. Some of them possess significant antibacterial activity against Gram-positive organisms (Staphylococcus aureus ATCC 25923 and Enterococcus faecalis ATCC 29212) but all are poorly active or inactive against Gram-negative organisms (Escherichia coli ATCC 25922 and Pseudomonas aeruginosa ATCC 27853). The compounds with the lowest minimal inhibitory concentrations (esters of 3-hydroxy succinimides) are also the most cytotoxic against green monkey Vero cell line (ATCC CCL-81) and could explain that perhaps apoptosis should be implicated in eukaryotic cell cytotoxicity of succinimides.
Assuntos
Antibacterianos/farmacologia , Succinimidas/farmacologia , Animais , Antibacterianos/síntese química , Chlorocebus aethiops , Enterococcus faecalis/efeitos dos fármacos , Escherichia coli/efeitos dos fármacos , Testes de Sensibilidade Microbiana , Pseudomonas aeruginosa/efeitos dos fármacos , Staphylococcus aureus/efeitos dos fármacos , Succinimidas/síntese química , Células VeroRESUMO
New structure-activity relationships of a series of methylene or side chain modified retinoids on NB4 acute promyelocytic leukemia cells are investigated. The differentiation- and apoptosis-inducing potential of these compounds is analyzed on the basis of their selective retinoic acid receptor binding profile.
Assuntos
Leucemia Promielocítica Aguda/patologia , Metano/análogos & derivados , Metano/química , Metano/farmacologia , Retinoides/química , Retinoides/farmacologia , Morte Celular , Diferenciação Celular , Linhagem Celular Tumoral , Humanos , Hidrocarbonetos , Relação Estrutura-AtividadeRESUMO
In the field of our research programs concerning novel antimicrobial agents, a series of N-substituted imides was synthesized. These compounds were obtained by cyclization of amido-acids in acetic anhydride/sodium acetate or hexamethyldisilazane/zinc bromide for the hydroxy-aromatic derivatives. The hydroxy-alkyl maleimides were directly prepared by condensation of the corresponding amino-alcohol with maleic anhydride in boiling toluene. Most of N-substituted maleimides showed an interesting antimicrobial activity towards bacteria from the ATCC collection (Staphylococcus aureus ATCC 25923, Enterococcus faecalis ATCC 29212, Escherichia coli ATCC 25922 and Pseudomonas aeruginosa ATCC 27853) but the MIC values for P. aeruginosa were always high (128 microg/ml). The imides with alkyl substituents showed higher activities than aromatic analogues with MIC values in the range of 8-32 microg/ml. Comparatively, succinimides were practically inactive.
