- Design, synthesis and antifungal activity of novel selenochroman-4-one derivatives
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A series of novel selenochroman-4-one derivatives bearing semicarbazone or nitrogen heterocycle was designed, synthesized, tested antifungal activity and characterized via 1H-NMR, 13C-NMR, and HRMS. The design of the compounds is based on the principle of molecule hybrid and bioisosterism. We aimed at attaching semicarbazones or nitrogen heterocycle to the selenochroman-4-one for enhancing antifungal activity. The antifungal activity of target compounds was evaluated using the microdilution broth method in vitro test. Bioassay results indicated that some of the derivatives displayed good fungistatic activity on Candida zeylanoides, Candida albicans, Cryptococcus neoformans, resistant to fluconazole strain 103 (Candida albicans), resistant to fluconazole strain 100 (Candida albicans) and strain SC5314 (Candida albicans). All the compounds exhibit antifungal activities against the tested funguses in different levels, among them, 7 compounds of antifungal activity against several funguses is better than that of the control drug fluconazole. Based on the results, preliminary structure activity relationships (SARs) were summarized to serve as a foundation for further investigation.
- Xu, Hang,Hu, Yu-Kun,Guo, Meng-Bi,Huang, Ai-Su,Su, Xin,Guo, Chun
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p. 2455 - 2463
(2017/10/06)
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- Inhibition of monoamine oxidase by 8-phenoxymethylcaffeine derivatives
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A recent study has reported that a series of 8-benzyloxycaffeines are potent and reversible inhibitors of both human monoamine oxidase (MAO) isoforms, MAO-A and -B. In an attempt to discover additional caffeine derivatives with potent MAO inhibitory activities, and to contribute to the known structure-activity relationships of MAO inhibition by caffeine derived compounds, the present study investigates the MAO inhibitory potencies of series of 8-phenoxymethylcaffeine and 8-[(phenylsulfanyl)methyl]caffeine derivatives. The results document that the 8-phenoxymethylcaffeine derivatives act as potent reversible inhibitors of MAO-B, with IC50 values ranging from 0.148 to 5.78 μM. In contrast, the 8-[(phenylsulfanyl)methyl]caffeine derivatives were found to be weak inhibitors of MAO-B, with IC50 values ranging from 4.05 to 124 μM. Neither the 8-phenoxymethylcaffeine nor the 8-[(phenylsulfanyl)methyl]caffeine derivatives exhibited high binding affinities for MAO-A. While less potent than the 8-benzyloxycaffeines as MAO-B inhibitors, this study concludes that 8-phenoxymethylcaffeines may act as useful leads for the design of MAO-B selective inhibitors. Such compounds may find application in the therapy of neurodegenerative disorders such as Parkinson's disease. Using molecular docking experiments, this study also proposes possible binding orientations of selected caffeine derivatives in the active sites of MAO-A and -B.
- Okaecwe, Thokozile,Swanepoel, Abraham J.,Petzer, Anél,Bergh, Jacobus J.,Petzer, Jacobus P.
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experimental part
p. 4336 - 4347
(2012/08/28)
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