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이상광,박민균,장호은,이진주,남기평,조대원,나춘섭,Kamil Musilek,Anna Horova,Jan Korabecny,Rafael Dolezal,Daniel Jun,Kamil Kuca* 대한화학회 2015 Bulletin of the Korean Chemical Society Vol.36 No.6
Novel types of symmetric bis-7-methoxytacrines connected by oligoethyleneoxy chains 3–5 and nonsymmetric monomeric 7-methoxytacrines containing hydroxyl-terminated oligoethyleneoxy chains 6–8 were prepared, and their in vitro/in silico effects on human recombinant AChE (hAChE) and human plasmatic butyrylcholinesterase (hBChE) were compared, with 7-MEOTA (2) as the standard compound. The symmetric bis-7-MEOTA derivatives 3–5 showed hAChE inhibition similar to that of 2. On the other hand, their effects on hBChE revealed an increasing inhibition trend when the oligoethyleneoxy units between the two 7-MEOTA moieties became longer. Accordingly, compounds 4 and 5 showed better selectivity towards hBChE. The most effective in the inhibition hAChE and hBChE was compound 8 with the longest oligoethyleneglycol chain, whereas compounds 6 and 7 resulted in similar IC50 values. A molecular modeling study using substrates 5 and 8 showed a possible binding conformation and protein–ligand interaction between the substrates and AChE/BChE.
Larik, Fayaz Ali,Faisal, Muhammad,Saeed, Aamer,Channar, Pervaiz Ali,Korabecny, Jan,Jabeen, Farukh,Mahar, Ihsan Ali,Kazi, Mehar Ali,Abbas, Qamar,Murtaza, Ghulam,Khan, Gul Shahzada,Hassan, Mubashir,Seo, Academic Press 2019 Bioorganic chemistry Vol.86 No.-
<P><B>Abstract</B></P> <P>The increasing resistance of pathogens to common antibiotics, as well as the need to control urease activity to improve the yield of soil nitrogen fertilization in agricultural applications, has stimulated the development of novel classes of molecules that target urease as an enzyme. In this context, the newly developed compounds on the basis of 1-heptanoyl-3-arylthiourea family were evaluated for Jack bean urease enzyme inhibition activity to validate their role as potent inhibitors of this enzyme. 1-Heptanoyl-3-arylthioureas were obtained in excellent yield and characterized through spectral and elemental analysis. All the compounds displayed remarkable potency against urease inhibition as compared to thiourea standard. It was found that novel compounds fulfill the criteria of drug-likeness by obeying Lipinski’s rule of five. Particularly compound <B>4a</B> and <B>4c</B> can serve as lead molecules in 4D (drug designing discovery and development). Kinetic mechanism and molecular docking studies also carried out to delineate the mode of inhibition and binding affinity of the molecules.</P> <P><B>Highlights</B></P> <P> <UL> <LI> A new family of 1-heptanoyl-3-arylthioureas (<B>4a-4j</B>) was synthesized in excellent yield. </LI> <LI> The synthesized 1-heptanoyl-3-arylthiourea family were evaluated for Jack bean urease enzyme inhibition activity. </LI> <LI> Particularly compound <B>4a</B> and <B>4c</B> can serve as lead molecules in 4D (drug designing discovery and development). </LI> <LI> Kinetic mechanism and molecular docking studies also carried out to delineate the mode of inhibition and binding affinity. </LI> </UL> </P> <P><B>Graphical abstract</B></P> <P>[DISPLAY OMISSION]</P>