. 67,481 (1989).The causative agent of toxicity in cultured mussels from a localized area of eastern Prince Edward Island has been identified as domoic acid, a neuroexcitatory amino acid. The toxin was isolated by a number of different bioassay-directed separation techniques including high-performance liquid chromatography, high-voltage paper electrophoresis, and ion-exchange chromatography, and characterized by a number of spectroscopic techniques including ultraviolet, infrared, mass spectrometry, and nuclear magnetic resonance. The isolation and purification methods are described in detail and some new analytical data for domoic acid are reported. On a identifie l'agent qui est la cause de la toxicit6 des moules d7Clevage provenant d'une zone localisCe de la portion est de l'ile du prince Edouard; il s'agit de l'acide domoi'que, un acide amink neuro-excitant. On a is016 la toxine en faisant appel L un certain nombre de techniques de skparation basCes sur des essais biologiques parmi lesquelles on peut citer la chromatographie liquide B haute performance, 1'Clectrophorkse sur papier B voltage ClevC ainsi que la chromatographie d'Cchange ionique; on l'a caractCrisCe par un certain nombre de techniques spectroscopiques dont I'ultraviolette, l'infrarouge, la spectromCtrie de masse et la rtsonance magnCtique nuclkaire. On dCcrit en detail les mCthodes d'isolement et de purification et on prksente des donnCes analytiques nouvelles concernant I'acide domoi'que.Mots cle's : toxine des coquillages, acide domoi'que, neurotoxine, analyse baste sur des essais biologiques.[Traduit par la revue]

No abstract

No abstract

Development of new antimycobacterial agents for Mycobacterium avium complex (MAC) infections is important particularly for persons coinfected with human immunodeficiency virus. The objectives of this study were to evaluate the in vitro activity of 2,4-diamino-5-methyl-5-deazapteridines (DMDPs) against MAC and to assess their activities against MAC dihydrofolate reductase recombinant enzyme (rDHFR). Seventy-seven DMDP derivatives were evaluated initially for in vitro activity against one to three strains of MAC (NJ168, NJ211, and/or NJ3404). MICs were determined with 10-fold dilutions of drug and a colorimetric (Alamar Blue) microdilution broth assay. MAC rDHFR 50% inhibitory concentrations versus those of human rDHFR were also determined. Substitutions at position 5 of the pteridine moiety included ™CH 3 , ™CH 2 CH 3 , and ™CH 2 OCH 3 groups. Additionally, different substituted and unsubstituted aryl groups were linked at position 6 through a two-atom bridge of either ™CH 2 NH, ™CH 2 N(CH 3 ), ™CH 2 CH 2 , or ™CH 2 S. All but 4 of the 77 derivatives were active against MAC NJ168 at concentrations of <13 g/ml. Depending on the MAC strain used, 81 to 87% had MICs of <1.3 g/ml. Twenty-one derivatives were >100-fold more active against MAC rDHFR than against human rDHFR. In general, selectivity was dependent on the composition of the two-atom bridge at position 6 and the attached aryl group with substitutions at the 2 and 5 positions on the phenyl ring. Using this assessment, a rational synthetic approach was implemented that resulted in a DMDP derivative that had significant intracellular activity against a MAC-infected Mono Mac 6 monocytic cell line. These results demonstrate that it is possible to synthesize pteridine derivatives that have selective activity against MAC.

No abstract