- Potent arylamide derivatives as dual-target antifungal agents: Design, synthesis, biological evaluation, and molecular docking studies
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Fungal infections have become a serious medical problem due to the high infection rate and the frequent emergence of drug resistance. Ergosterol is an important structural component of the fungal cell membrane, its synthetases (squalene epoxidase (SE) and 14α-demethylase (CYP51)) are considered as the key points to block the ergosterol synthesis. In this study, we designed a series of dual-target arylamides derivatives based on the analysis of active sites (SE, CYP51). Subsequently, these target compounds were synthesized, and their antifungal activity was evaluated. Most of compounds demonstrate the potent antifungal activity against multiple Candida spp. and A. fum. In particular, the antifungal activities of compounds 10b and 11c are not only superior to positive control drugs, but also have significant inhibitory effects on drug-resistant fungi (C.alb. Strain100, C.alb. Strain103). Therefore, their action mechanism was further studied. Cellular uptake and electron microscopy observation showed that target compounds were able to enter fungal cytoplasmic region through free diffusion, and destroyed cell membrane structure. At the same time, preliminary mechanisms have demonstrated that they can affect the synthesis of ergosterol by inhibiting the activity of dual targets. It is worth noting that they also can exhibit excellent antifungal activity and low toxic side effects in vivo. Their ADMET properties and binding models were established will be useful for further lead optimization.
- An, Yunfei,Dong, Yue,Han, Jun,Liu, Min,Liu, Xinyong,Sun, Bin
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- Palladium(II)-catalyzed one-pot enantioselective synthesis of arylglycine derivatives from ethyl glyoxylate, p-toluenesulfonyl isocyanate and arylboronic acids
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A palladium(II)-catalyzed, one-pot enantioselective synthesis of arylglycine derivatives from ethyl glyoxylate, p-toluenesulfonyl isocyanate and arylboronic acids giving moderate to good yields and enantioselectivity has been developed. This reaction prov
- Dai, Huixiong,Yang, Miao,Lu, Xiyan
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supporting information; experimental part
p. 249 - 253
(2009/04/11)
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- Asymmetric synthesis of protected arylglycines by rhodium-catalyzed addition of arylboronic acids to N-tert-butanesulfinyl imino esters
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A new method for the Rh(I)-catalyzed addition of arylboronic acids to N-tert-butanesulfinyl imino esters has been developed for the asymmetric synthesis of arylglycine derivatives. This method provides high yields (61-90%) and diastereoselectivities (>98:2) for a variety of functionalized arylboronic acids. The N-sulfinyl arylglycine ester products are versatile intermediates for further transformations, including selective protecting group removal, conversion to β-amino alcohols, and direct incorporation into peptides. Copyright
- Beenen, Melissa A.,Weix, Daniel J.,Ellman, Jonathan A.
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p. 6304 - 6305
(2007/10/03)
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- Isozyme-specific glutathione-S-transferase inhibitors: Design and synthesis
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Glutathione-S-transferase (GST) isozyme-selective inhibitors were designed by an empirically guided strategy. In the first phase, literature data were used to select C-terminal modifications which generated maximum variation in the catalytic efficiency (V
- Lyttle,Hocker,Hui,Caldwell,Aaron,Engqvist- Goldstein,Flatgaard,Bauer
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p. 189 - 194
(2007/10/02)
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