Abstract：
:Molecules capable of engaging with multiple targets associated with pathological condition of Alzheimer's disease have proved to be potential anti-Alzheimer's agents. In our goal to develop multitarget-directed ligands for the treatment of Alzheimer's disease, a novel series of carbazole-based stilbene derivatives were designed by the fusion of carbazole ring with stilbene scaffold. The designed compounds were synthesized and evaluated for their anti-AD activities including cholinesterase inhibition, Aβ aggregation inhibition, antioxidant and metal chelation properties. Amongst them, (E)-1-(4-(2-(9-ethyl-9H-carbazol-3-yl)vinyl)phenyl)-3-(2-(pyrrolidin-1-yl)ethyl)thiourea (50) appeared to be the best candidate with good inhibitory activities against AChE (IC50 value of 2.64 μM) and BuChE (IC50 value of 1.29 μM), and significant inhibition of self-mediated Aβ1-42 aggregation (51.29% at 25 μM concentration). The metal chelation study showed that compound (50) possessed specific copper ion chelating property. Additionally, compound (50) exhibited moderate antioxidant activity. To understand the binding mode of 50, molecular docking studies were performed, and the results indicated strong non-covalent interactions of 50 with the enzymes in the active sites of AChE, BuChE as well as of the Aβ1-42 peptide. Additionally, it showed promising in silico ADMET properties. Putting together, these findings evidently showed compound (50) as a potential multitarget-directed ligand in the course of developing novel anti-AD drugs.
journal_name
Bioorg Chemjournal_title
Bioorganic chemistryauthors
Patel DV,Patel NR,Kanhed AM,Teli DM,Patel KB,Joshi PD,Patel SP,Gandhi PM,Chaudhary BN,Prajapati NK,Patel KV,Yadav MRdoi
10.1016/j.bioorg.2020.103977subject
Has Abstractpub_date
2020-08-01 00:00:00pages
103977eissn
0045-2068issn
1090-2120pii
S0045-2068(20)31113-5journal_volume
101pub_type
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