Your browser doesn't support javascript.
loading
Show: 20 | 50 | 100
Results 1 - 3 de 3
Filter
Add more filters










Database
Language
Publication year range
1.
Eur J Med Chem ; 43(6): 1336-43, 2008 Jun.
Article in English | MEDLINE | ID: mdl-17949859

ABSTRACT

In order to explore the antiproliferative effect associated with the xanthone framework, several arylhydrazonomethyl derivatives were synthesized from various isomeric 1,3-dihydroxyxanthone carbaldehydes. Variation in the position of the aldehydic function led to three sets of compounds, bearing the hydrazonomethyl chain at positions 5, 6 or 7 on the xanthone nucleus, respectively. The antiproliferative effect of the compounds was evaluated in vitro using the MTT colorimetric method against two human cancer cell lines (MCF-7, breast adenocarcinoma, and KB 3.1, squamous cell oral carcinoma) for two time periods (24 h and 72 h). Among the series, four compounds exhibited interesting growth inhibitory effects against both the cell lines, with IC(50) values in the micromolar concentration range. When compared with doxorubicin, the xanthone derivatives showed moderate cytotoxic effects. Surprisingly, unlike doxorubicin, these compounds displayed no significant time-dependent change in the concentration causing 50% inhibitory effect in proliferation. This unusual cytotoxicity profile led to the hypothesis that these molecules could be endowed with a mechanism of action distinct to that of doxorubicin.


Subject(s)
Aldehydes/chemical synthesis , Aldehydes/pharmacology , Cell Proliferation/drug effects , Hydrazones/chemical synthesis , Hydrazones/pharmacology , Aldehydes/chemistry , Cell Line, Tumor , Humans , Hydrazones/chemistry , Magnetic Resonance Spectroscopy , Spectrophotometry, Infrared
2.
J Enzyme Inhib Med Chem ; 22(5): 620-31, 2007 Oct.
Article in English | MEDLINE | ID: mdl-18035830

ABSTRACT

The synthesis of new 4-[2-(alkylamino)ethylthio]pyrrolo[1,2-a]quinoxaline derivatives la-1 is described in five or six steps starting from various substituted nitroanilines 2a-e. The bioisostere 5-[2-(alkylamino)ethylthio]pyrrolo[1,2- a]thieno[3,2-e]pyrazine 1m was also prepared. The new derivatives were evaluated as efflux pump inhibitors (EPIs) in a model targeting the NorA system of Staphylococcus aureus. The antibiotic susceptibility of two strains overproducing NorA, SA-1199B and SA-1, was determined alone and in combination with the neo-synthesised compounds by the agar diffusion method and MIC determination, in comparison with reserpine and omeprazole taken as reference EPIs. A preliminary structure-activity relationship study firstly allowed to clarify the influence of the substituents at positions 7 and/or 8 of the pyrrolo[1,2-a]quinoxaline nucleus. Methoxy substituted compounds, 1b and 1g, were more potent EPIs than the unsubstituted compounds (1a and 1f), followed by chlorinated derivatives (1c-d and 1h). Moreover, the replacement of the N,N-diethylamino group (compounds 1a-e) by a bioisostere such as pyrrolidine (compounds 1f-h) enhanced the EPI activity, in contrast with the replacement by a piperidine moiety (compounds 1i-k). Finally, the pyrrolo[1,2-a]thieno[3,2-e]pyrazine compound 1m exhibited a higher EPI activity than its pyrrolo[1,2-a]quinoxaline analogue la, opening the way to further pharmacomodulation.


Subject(s)
Bacterial Proteins/antagonists & inhibitors , Drug Resistance, Multiple, Bacterial/drug effects , Multidrug Resistance-Associated Proteins/antagonists & inhibitors , Pyrazines/chemical synthesis , Pyrazines/pharmacology , Quinoxalines/chemical synthesis , Quinoxalines/pharmacology , Staphylococcus aureus/drug effects , Microbial Sensitivity Tests , Molecular Structure , Pyrazines/chemistry , Quinoxalines/chemistry
3.
Eur J Med Chem ; 37(3): 237-53, 2002 Mar.
Article in English | MEDLINE | ID: mdl-11900868

ABSTRACT

A series of arylhydrazones derived from various 6,8-diacetoxy- or 6,8-dihydroxy-9-oxo-9H-xanthene carboxaldehydes were synthesized and evaluated for their in vitro antifungal properties against two human pathogenic yeasts (Candida albicans and C. krusei) according to a diffusion method. The activity was strongly dependent from the position of the (1-arylhydrazinyl-2-ylidene)methyl chain in the xanthone molecular skeleton. Compounds having the nitrogen side chain in the 4-position, with a further halogen substitution on the terminal phenyl ring showed fungistatic effects. Within this series, the 4-fluorophenylhydrazinyl derivative 13g exhibited the highest activity, particularly against C. krusei, with a greater efficacy than that of econazole, used as reference.


Subject(s)
Antifungal Agents/chemical synthesis , Antifungal Agents/pharmacology , Candida/drug effects , Xanthenes/chemical synthesis , Xanthenes/pharmacology , Xanthones , Antifungal Agents/chemistry , Microbial Sensitivity Tests , Molecular Structure , Structure-Activity Relationship , Xanthenes/chemistry
SELECTION OF CITATIONS
SEARCH DETAIL
...