Cytotoxicity of 3,4-dihalogenated 2(5H)-furanones

Mucohalogen acids have been used for the preparation of a variety of 3,4-clihalogenated 2(5H)-furanones. In one synthetic step the carbarnates 2a-c and the pseudoanhydrides 4a-e were prepared using isocyanates and acid anhydrides. A series of 5-alkoxylated 3,4-dichloro-2(5H)-furanones 5a-o have been synthesized with a wide range of lipophilicity, using the hydroxy-form of mucohalogen acids 1a and 1b. The 5-allyl-3,4-dichloro-2(5H)-furanone 5f was derived into the dihydro-isoxazol 6 and the oxirane 7. The methyl ester 5a was converted with ammonia into the tetramic acid chloride 11. The pseudo acid chloride 3 was reacted further into the bis aziricline 8. Reduction of the mucochloric acid 1a furnished the trichlorofuranone 3. The cytotoxicity of these simple and bis-cyclic butenolides have been evaluated in tissue culture on MAC13 and MAC16 cancer cell lines using the MTT cytotoxicity assay. The ester 5g, the acetate 4b and the carbamate 2b displayed a cytotoxicity in the low micromolar range. Further, an IC50 (50% inhibitory concentration) of 50 nM and 30 nm was determined forthe epoxide 7 and the aziridine 18. © 2004 The Authors Recieved.

Build-up and resetting of auditory stream segregation in quiet and in complex-tone backgrounds

Thirteen experiments investigated the dynamics of stream segregation. Experiments 1-6b used a similar method, where a same-frequency induction sequence (usually 10 repetitions of an identical pure tone) promoted segregation in a subsequent, briefer test sequence (of alternating low- and high-frequency tones). Experiments 1-2 measured streaming using a direct report of perception and a temporal-discrimination task, respectively. Creating a single deviant by altering the final inducer (e.g. in level or replacement with silence) reduced segregation, often substantially. As the prior inducers remained unaltered, it is proposed that the single change actively reset build-up. The extent of resetting varied gradually with the size of a frequency change, once noticeable (experiments 3a-3b). By manipulating the serial position of a change, experiments 4a-4b demonstrated that resetting only occurred when the final inducer was replaced with silence, as build-up is very rapid during a same-frequency induction sequence. Therefore, the observed resetting cannot be explained by fewer inducers being presented. Experiment 5 showed that resetting caused by a single deviant did not increase when prior inducers were made unpredictable in frequency (four-semitone range). Experiments 6a-6b demonstrated that actual and perceived continuity have a similar effect on subsequent streaming judgements promoting either integration or segregation, depending on listening context. Experiment 7 found that same-frequency inducers were considerably more effective at promoting segregation than an alternating-frequency inducer, and that a trend for deviant-tone resetting was only apparent for the same-frequency case. Using temporal-order judgments, experiments 8-9 demonstrated the stream segregation of pure-tone-like percepts, evoked by sudden changes in amplitude or interaural time difference for individual components of a complex tone, Active resetting was observed when a deviant was inserted into a sequence of these percepts (Experiment 10). Overall, these experiments offer new insight into the segregation-promotIng effect of induction sequences, and the factors which can reset this effect.