Four core structures capable of providing sub-nanomolar inhibitors of anthrax lethal factor (LF) were evaluated by comparing the potential for toxicity, physicochemical properties, in vitro ADME profiles, and relative efficacy in a rat lethal toxin (LT) model of LF intoxication. Poor efficacy in the rat LT model exhibited by the phenoxyacetic acid series (3) correlated with low rat microsome and plasma stability. Specific molecular interactions contributing to the high affinity of inhibitors with a secondary amine in the C2-side chain were revealed by x-ray crystallography.
A total of 16 male blue gouramis Trichogaster trichopterus were gonadectomized and, 1 month after the operation, tested for reproductive behavior. Eleven of the 16 castrates failed to build nests or go through the prespawning and spawning procedures typical of intact fish. When placed with intact or castrated males they fought as vigorously as normal males until a dominance relationship was established. These males carried relatively short rounded dorsal fins and remained pale compared to intact males.Five castrated males built nests and spawned, and initially cared for inviable eggs. These fish possessed dorsal fins similar in length to intact males.Testosterone treatment resulted in a restoration of nest-building and spawning behavior and an elongation of the dorsal fin in castrated males which had previously failed to spawn.It is concluded that in the blue gourami reproductive behavior and secondary sexual characteristics are under the control of the gonadal hormones. The persistence of sexual behavior in five of the castrates was probably due to undetected regeneration or, less likely, to an extragonadal source of androgen. Agonistic behavior other than that involved in the defence of a territory is apparently unaffected by castration.
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