FRINK Linked Data Fragments server

Matches in SemOpenAlex for { <https://semopenalex.org/work/W3190494224> ?p ?o ?g. }

• W3190494224 endingPage "113735" @default.
• W3190494224 startingPage "113735" @default.
• W3190494224 abstract "Cannabidiol (CBD) and rivastigmine have been launched as drugs for treating dementia and cholinesterases (ChEs) are ideal drug targets. This study focused on developing novel ChE inhibitors as drug leads against dementia through molecular modeling and fragment reassembly approaches. A potent carbamate fragment binding to active site gorge of BuChE was found via a docking-based structural splicing approach, thus, 17 novel compounds were designed by structural reassembly. Compound C16 was identified as a highly selective potent BuChE inhibitor (IC 50 = 5.3 nM, SI > 4000), superior to CBD (IC 50 = 0.67 μM). C16 possessed BBB penetrating ability, benign safety, neuroprotection, antioxidant and pseudo-irreversible BuChE inhibition ( K d = 13 nM, k 2 = 0.26 min −1 ), showing good drug-like properties. In vivo studies confirmed that C16 significantly ameliorated the scopolamine-induced cognition impairment, almost entirely recovered the A β 1−42 (icv)-impaired cognitive function to the normal level, showed better behavioral performance than donepezil and good anti-amyloidogenic effect. Hence, the potential BuChE inhibitor C16 can be developed as a promising disease-modifying treatment of AD. Cannabidiol-carbamate hybrids were designed via a docking-based structural splicing approach and identified as highly selective potent BuChE inhibitors. C16 with good drug-like properties showed better behavioral performance than donepezil and good anti-amyloidogenic effect for the treatment of Alzheimer's disease. • Lead discovery by molecular modeling and fragment reassembly. • Cannabidiol−carbamate hybrids as selective potent BuChE inhibitors. • IC 50 values of C16 and CBD are 5.3 and 670 nM for BuChE, respectively. • C16 showed mild antioxidant capacity (27.1% for DPPH). • C16 almost entirely recovered the A β 1−42 (icv)-impaired cognitive function." @default.
• W3190494224 created "2021-08-16" @default.
• W3190494224 creator A5009575321 @default.
• W3190494224 creator A5017947172 @default.
• W3190494224 creator A5025940317 @default.
• W3190494224 creator A5031888438 @default.
• W3190494224 creator A5033111996 @default.
• W3190494224 creator A5037935776 @default.
• W3190494224 creator A5064071078 @default.
• W3190494224 creator A5064817667 @default.
• W3190494224 creator A5074783604 @default.
• W3190494224 creator A5084185565 @default.
• W3190494224 creator A5088923696 @default.
• W3190494224 date "2021-11-01" @default.
• W3190494224 modified "2023-10-16" @default.
• W3190494224 title "Novel cannabidiol−carbamate hybrids as selective BuChE inhibitors: Docking-based fragment reassembly for the development of potential therapeutic agents against Alzheimer's disease" @default.
• W3190494224 cites W1977748011 @default.
• W3190494224 cites W1980794050 @default.
• W3190494224 cites W1988940766 @default.
• W3190494224 cites W1992858776 @default.
• W3190494224 cites W2013785494 @default.
• W3190494224 cites W2022847865 @default.
• W3190494224 cites W2038211199 @default.
• W3190494224 cites W2047434405 @default.
• W3190494224 cites W2051992129 @default.
• W3190494224 cites W2067174909 @default.
• W3190494224 cites W2073997738 @default.
• W3190494224 cites W2085638132 @default.
• W3190494224 cites W2096597937 @default.
• W3190494224 cites W2100641353 @default.
• W3190494224 cites W2118117906 @default.
• W3190494224 cites W2147993766 @default.
• W3190494224 cites W2149110258 @default.
• W3190494224 cites W2159866533 @default.
• W3190494224 cites W2161470962 @default.
• W3190494224 cites W2281220653 @default.
• W3190494224 cites W2412804379 @default.
• W3190494224 cites W2435165854 @default.
• W3190494224 cites W2462451779 @default.
• W3190494224 cites W2463644552 @default.
• W3190494224 cites W2730737869 @default.
• W3190494224 cites W2743038704 @default.
• W3190494224 cites W2744937512 @default.
• W3190494224 cites W2770148668 @default.
• W3190494224 cites W2773982889 @default.
• W3190494224 cites W2775477342 @default.
• W3190494224 cites W2803569743 @default.
• W3190494224 cites W2804633924 @default.
• W3190494224 cites W2805257646 @default.
• W3190494224 cites W2885700455 @default.
• W3190494224 cites W2887638272 @default.
• W3190494224 cites W2895355796 @default.
• W3190494224 cites W2897804429 @default.
• W3190494224 cites W2898588332 @default.
• W3190494224 cites W2902814700 @default.
• W3190494224 cites W2905678168 @default.
• W3190494224 cites W2940010989 @default.
• W3190494224 cites W2945212355 @default.
• W3190494224 cites W2953282350 @default.
• W3190494224 cites W2963392042 @default.
• W3190494224 cites W2965523056 @default.
• W3190494224 cites W2969222286 @default.
• W3190494224 cites W2970154925 @default.
• W3190494224 cites W2974747000 @default.
• W3190494224 cites W2980601903 @default.
• W3190494224 cites W2996080671 @default.
• W3190494224 cites W3004639316 @default.
• W3190494224 cites W3008429437 @default.
• W3190494224 cites W3008650933 @default.
• W3190494224 cites W3016880461 @default.
• W3190494224 cites W3033694221 @default.
• W3190494224 cites W3035656313 @default.
• W3190494224 cites W3046194558 @default.
• W3190494224 cites W3056226553 @default.
• W3190494224 cites W3080512164 @default.
• W3190494224 cites W3080926882 @default.
• W3190494224 cites W3092252615 @default.
• W3190494224 cites W3106840706 @default.
• W3190494224 cites W3113764084 @default.
• W3190494224 cites W3127459568 @default.
• W3190494224 doi "https://doi.org/10.1016/j.ejmech.2021.113735" @default.
• W3190494224 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/34371367" @default.
• W3190494224 hasPublicationYear "2021" @default.
• W3190494224 type Work @default.
• W3190494224 sameAs 3190494224 @default.
• W3190494224 citedByCount "18" @default.
• W3190494224 countsByYear W31904942242022 @default.
• W3190494224 countsByYear W31904942242023 @default.
• W3190494224 crossrefType "journal-article" @default.
• W3190494224 hasAuthorship W3190494224A5009575321 @default.
• W3190494224 hasAuthorship W3190494224A5017947172 @default.
• W3190494224 hasAuthorship W3190494224A5025940317 @default.
• W3190494224 hasAuthorship W3190494224A5031888438 @default.
• W3190494224 hasAuthorship W3190494224A5033111996 @default.
• W3190494224 hasAuthorship W3190494224A5037935776 @default.
• W3190494224 hasAuthorship W3190494224A5064071078 @default.
• W3190494224 hasAuthorship W3190494224A5064817667 @default.
• W3190494224 hasAuthorship W3190494224A5074783604 @default.

• next