- Discovery of a dual tubulin polymerization and cell division cycle 20 homologue inhibitor via structural modification on apcin
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Apcin is one of the few compounds that have been previously reported as a Cdc20 specific inhibitor, although Cdc20 is a very promising drug target. We reported here the design, synthesis, and biological evaluations of 2,2,2-trichloro-1-aryl carbamate derivatives as Cdc20 inhibitors. Among these derivatives, compound 9f was much more efficient than the positive compound apcin in inhibiting cancer cell growth, but it had approximately the same binding affinity with apcin in SPR assays. It is possible that another mechanism of action might exist. Further evidence demonstrated that compound 9f also inhibited tubulin polymerization, disorganized the microtubule network, and blocked the cell cycle at the M phase with changes in the expression of cyclins. Thus, it induced apoptosis through the activation of caspase-3 and PARP. In addition, compound 9f inhibited cell migration and invasion in a concentration-dependent manner. These results provide guidance for developing the current series as potential new anticancer therapeutics.
- Huang, Pan,Le, Xiangyang,Huang, Fei,Yang, Jie,Yang, Haofeng,Ma, Junlong,Hu, Gaoyun,Li, Qianbin,Chen, Zhuo
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p. 4685 - 4700
(2020/06/08)
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- Process for formulating a synthetic drug for use in animal feed, and resulting formulation
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A method of formulating a synthetic drug for use in animal feed, for the purpose of reducing carry-over of the synthetic drug to subsequent lots of animal feed in the feed mill.
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- Chemotherapeutically active nitro compounds. 4,5-Nitroimidazoles (part III)
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More than 100 1-methyl-5-nitroimidazoles substituted in the 2-position via an oxymethyl group were synthesized and their structure-activity relationship toward various protozoa was investigated. Among the derivatives substituted with an aromatic radical there are most of the compounds which are highly effective against trichomonads; 9 preparations are superior to tinidazole and 29 are superior to metronidazole in mice infected with Trichomonas fetus and 9 compounds exhibit a better effect than metronidazole in golden hamsters intrahepatically infected with Entamoeba histolytica. In the same series one dialkylamino-acetamide derivative shows excellent trypanocidal activity in the NMRI mouse, but this effect is limited to Trypanosoma brucei; 12 preparations developed a trypanocidal effect only after relatively high doses; their range of efficacy included Trypanosoma cruzi, among others, after repeated treatment. Of the carboxyl acid, carbamic acid and sulphonic acid esters synthesized, only the already known group of carbamic acid esters possess a pronounced antiprotozoal effect. Among the preparations substituted with a heterocyclic radical some of the pyridine derivatives proved to have distinct trichomonacidal activity. The influence of the type of substitution and the stability of the C-X bond in 2-substituted 5-nitroimidazoles of all compounds synthesized so far (I-III, 4th report) are discussed in 2 tables.
- Winkelmann,Raether
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p. 739 - 749
(2007/10/05)
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