ABSTRACT
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).
Subject(s)
Antimalarials/chemical synthesis , Chalcone/chemical synthesis , Erythrocytes/parasitology , Plasmodium falciparum/drug effects , Retinoids/chemical synthesis , Animals , Antimalarials/chemistry , Antimalarials/pharmacology , Chalcone/analogs & derivatives , Chalcone/pharmacology , Humans , Inhibitory Concentration 50 , Malaria/blood , Malaria/drug therapy , Malaria/parasitology , Parasitemia/drug therapy , Plasmodium falciparum/growth & development , Plasmodium falciparum/metabolism , Retinoids/chemistry , Retinoids/pharmacologyABSTRACT
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.
Subject(s)
Anti-Bacterial Agents/pharmacology , Succinimides/pharmacology , Animals , Anti-Bacterial Agents/chemical synthesis , Chlorocebus aethiops , Enterococcus faecalis/drug effects , Escherichia coli/drug effects , Microbial Sensitivity Tests , Pseudomonas aeruginosa/drug effects , Staphylococcus aureus/drug effects , Succinimides/chemical synthesis , Vero CellsABSTRACT
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.
Subject(s)
Leukemia, Promyelocytic, Acute/pathology , Methane/analogs & derivatives , Methane/chemistry , Methane/pharmacology , Retinoids/chemistry , Retinoids/pharmacology , Cell Death , Cell Differentiation , Cell Line, Tumor , Humans , Hydrocarbons , Structure-Activity RelationshipABSTRACT
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.
