Vol.:(0123456789) 1 3 Molecular Diversity https://doi.org/10.1007/s11030-019-10008-x ORIGINAL ARTICLE Design and synthesis of benzodiazepine‑1,2,3‑triazole hybrid derivatives as selective butyrylcholinesterase inhibitors Mehrdad Mehrazar 1  · Mahdi Hassankalhori 2  · Mahsa Toolabi 3  · Fereshteh Goli 1  · Setareh Moghimi 1  · Hamid Nadri 4  · Syed Nasir Abbas Bukhari 5  · Loghman Firoozpour 1  · Alireza Foroumadi 3,6 Received: 20 June 2019 / Accepted: 18 October 2019 © Springer Nature Switzerland AG 2019 Abstract A new series of compounds based on benzodiazepine-1,2,3-triazole were synthesized and evaluated as cholinesterase inhibi- tors by Ellman’s method. The compounds proved to be selective inhibitors of butyrylcholinesterase (BuChE) over ace- tylcholinesterase. The most potent compound was 3,3-dimethyl-11-(3-((1-(4-nitrobenzyl)-1H-1,2,3-triazol-4-yl)methoxy) phenyl)-2,3,4,5,10,11-hexahydro-1H-dibenzo[b,e][1,4]diazepin-1-one, identifed as a submicromolar inhibitor of BuChE with IC 50 value of 0.2 µM. In addition, the amyloid-β self-aggregation evaluation studies for selected compounds showed potent inhibitory efects compared to donepezil. The docking and cell viability studies supported the potential of compound 9b-6 as signifcant BuChE inhibitor. Graphic abstract Keywords Alzheimer’s disease · Benzodiazepine · 1,2,3-Triazole · Butyrylcholinesterase inhibitor · Click chemistry Introduction Dementia is one of the most widespread illnesses, afect- ing the lives of millions of people around the world [1–3]. Alzheimer’s disease (AD) is a neurodegenerative, chronic, and progressive disease, associated with losses of mental capabilities in terms of memory and learning. These dis- abilities gradually lead to the tragic isolation of an individual Electronic supplementary material The online version of this article (https://doi.org/10.1007/s11030-019-10008-x) contains supplementary material, which is available to authorized users. * Loghman Firoozpour froozpour@gmail.com * Alireza Foroumadi aforoumadi@yahoo.com Extended author information available on the last page of the article