The b-carboline analogs as a potent inhibitor for Alzheimer's Disease, molecular docking and dynamics simulation study

The b-carboline scaffold are very potent for encouraging molecular interactions with a wide range of Alzheimer's target. Based on biological importance of carboline nucleus, we have designed a new series of carboline derivatives and screened them for acetyl cholinesterase and butyrylcholinesterase inhibition. The structural interpretation of the synthesized analogs was done by spectroscopic techniques such as 1H NMR,13C NMR. Almost all analogs of the series exhibited good to moderate inhibition activities. The most potent analog among the series was analog 2 having, three hydroxyl groups on the phenyl ring. The IC50 values for this analog was 0.10 +/- 0.01 for acetylcholinesterase and 0.30 +/- 0.01 for butyrylcholinesterase. To understand the interactions of this analogs with the active sites of enzyme docking study was also carried out. (c) 2023 The Author(s). Published by Elsevier B.V. on behalf of King Saud University. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

Automated summary

The b-carboline scaffold is highly effective in promoting the molecular interactions with various Alzheimer's disease targets. A new series of carboline derivatives were designed based on the biological importance of the carboline nucleus, and were tested for their inhibition of acetylcholinesterase and butyrylcholinesterase. The synthesized analogs were analyzed using spectroscopic techniques, and most of them exhibited good to moderate inhibition activities. The most potent analog in the series, analog 2, showed significant inhibition of both acetylcholinesterase and butyrylcholinesterase. Docking studies were conducted to understand the interaction between this analog and the active sites of the enzymes.