Version 1
: Received: 2 October 2024 / Approved: 3 October 2024 / Online: 3 October 2024 (10:55:40 CEST)
How to cite:
Mlakić, M.; Ratajec, M.; Ratković, A.; Raspudić, A.; Baric, D.; Šagud, I.; Lasić, Z.; Odak, I.; Škorić, I. Efficient Access to New Structures with Incorporated 1,2,3-Triazolium Salts as Preferred Dual Cholinesterase Inhibitors. Preprints2024, 2024100229. https://doi.org/10.20944/preprints202410.0229.v1
Mlakić, M.; Ratajec, M.; Ratković, A.; Raspudić, A.; Baric, D.; Šagud, I.; Lasić, Z.; Odak, I.; Škorić, I. Efficient Access to New Structures with Incorporated 1,2,3-Triazolium Salts as Preferred Dual Cholinesterase Inhibitors. Preprints 2024, 2024100229. https://doi.org/10.20944/preprints202410.0229.v1
Mlakić, M.; Ratajec, M.; Ratković, A.; Raspudić, A.; Baric, D.; Šagud, I.; Lasić, Z.; Odak, I.; Škorić, I. Efficient Access to New Structures with Incorporated 1,2,3-Triazolium Salts as Preferred Dual Cholinesterase Inhibitors. Preprints2024, 2024100229. https://doi.org/10.20944/preprints202410.0229.v1
APA Style
Mlakić, M., Ratajec, M., Ratković, A., Raspudić, A., Baric, D., Šagud, I., Lasić, Z., Odak, I., & Škorić, I. (2024). Efficient Access to New Structures with Incorporated 1,2,3-Triazolium Salts as Preferred Dual Cholinesterase Inhibitors. Preprints. https://doi.org/10.20944/preprints202410.0229.v1
Chicago/Turabian Style
Mlakić, M., Ilijana Odak and Irena Škorić. 2024 "Efficient Access to New Structures with Incorporated 1,2,3-Triazolium Salts as Preferred Dual Cholinesterase Inhibitors" Preprints. https://doi.org/10.20944/preprints202410.0229.v1
Abstract
In previous research, 1,2,3-triazolium salts showed significant biological activity as potential in-hibitors of the enzymes cholinesterases (ChEs), crucial for neurotransmission. In this research, pairs of uncharged thienobenzo-triazoles and their charged salts were prepared in order to ex-amine further the role of the positive charge on the nitrogen of the triazole ring on the interac-tions in the active site of the enzymes and to compare the selectivity of 1,2,3-triazolium salts in relation to their uncharged analogs obtained by photochemical cyclization. Neutral thienoben-zo-triazoles showed very good selective activity toward butyrylcholinesterase (BChE), while their salts showed excellent non-selective inhibition toward both BChE (the most active 23: IC50 0.47 mikroM) and acetylcholinesterase (AChE) enzymes (the most active 23: IC50 4.4 mikroM). These new structures with incorporated 1,2,3-triazolium salts present the new scaffold for drug development as it is known that the current therapy in Alzheimer's disease (AD) are selective AChE inhibitors, while in Parkinson's and all stages of AD, non-selective inhibitors of ChEs are preferred. Molecular docking of the selected compounds and their corresponding salts into the active sites of ChEs was conducted to identify the interactions responsible for the stability of the non-covalent cholinesterase-ligand complexes. As genotoxicity studies are crucial when devel-oping new active substances and finished drug forms, in silico studies for all the synthesized compounds have shown that compound 18 is the most promising candidate for genotoxic safety.
Medicine and Pharmacology, Medicine and Pharmacology
Copyright:
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
