In the self‐fertilizing hermaphroditic fish, Rivulus marmoratus, the susceptibility to tumor induction by N‐methyl‐N‐nitro‐N‐nitrosoguanidine(MNNG) was evaluated. Seven‐day‐old fish larvaewere exposed for 2 h toMNNG at concentrations ranging from 5 to 25 ppm in a static water bath. The exposed fish were observed at 2 and 4 monthsafter carcinogen treatmentto assess tumor development. Within 4‐ months after25 ppmMNNG exposure, nearly all fish developed thyroid tumors. The tumor incidenceswere dose‐ and time‐dependent, and the latent period of tumor induction was less than 2 months. Most induced neoplasms were papillary carcinomas similar histologically to those of rodents and humans, and the tumors were serially transplantable to other fish of the same species. These results demonstratethat rivulus could be useful as a model of thyroid carcinogenesis.
A novel phosphodiesterase-5 (PDE-5) inhibitor was found in a natural health food product. The previously unknown sildenafil analogue was isolated using preparative HPLC. The structure of the compound was elucidated using HPLC with diode array detection (DAD), time-of-flight mass spectrometry (TOF/MS), and nuclear magnetic resonance spectroscopy (NMR). An [M + H](+) ion was detected at m/z 505.2077 by LC-TOF/MS that was consistent with C23H32N6O3S2 (-0.98 ppm). By NMR analysis, the analogue was identified as 1-methyl-5-(5-(4-methylpiperazin-1-ylsulfonyl)-2-propoxyphenyl)-3-propyl-1H-pyrazolo[4,3-d]pyrimidine-7(6H)-thione. In this structure, the ethoxy group of thiosildenafil was substituted by a propoxy group of the unknown compound. Therefore, this novel thiosildenafil analogue was named propoxyphenyl thiosildenafil.
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