New naphtho/thienobenzo-triazoles with interconnected anti-inflammatory and cholinesterase inhibitory activity

  • Eur J Med Chem. 2022 Nov 5:241:114616. doi: 10.1016/j.ejmech.2022.114616.
Milena Mlakić  1 ,  Ilijana Odak  2 ,  Ivan Faraho  3 ,  Stanislava Talić  2 ,  Martina Bosnar  4 ,  Kornelija Lasić  5 ,  Danijela Barić  6 ,  Irena Škorić  7
Affiliations
  • 1. Department of Organic Chemistry, Faculty of Chemical Engineering and Technology, University of Zagreb, Marulićev trg 19, HR-10 000, Zagreb, Croatia.
  • 2. Department of Chemistry, Faculty of Science and Education, University of Mostar, Matice hrvatske bb, 88 000, Mostar, Bosnia and Herzegovina.
  • 3. Pharmacology in vitro, Selvita Ltd., Prilaz baruna Filipovića 29, HR-10 000, Zagreb, Croatia. Electronic address: [email protected].
  • 4. Pharmacology in vitro, Selvita Ltd., Prilaz baruna Filipovića 29, HR-10 000, Zagreb, Croatia.
  • 5. Teva api Chemical R&D, Pliva, Prilaz Baruna Filipovića 25, HR-10 000, Zagreb, Croatia.
  • 6. Group for Computational Life Sciences, Division of Physical Chemistry, Ruđer Bošković Institute, Bijenička cesta 54, HR-10 000, Zagreb, Croatia.
  • 7. Department of Organic Chemistry, Faculty of Chemical Engineering and Technology, University of Zagreb, Marulićev trg 19, HR-10 000, Zagreb, Croatia. Electronic address: [email protected].
PMID: 35870364 DOI: 10.1016/j.ejmech.2022.114616
Abstract

New 1,2,3-triazolo(thieno)Stilbenes were synthesized by Wittig reaction and photochemically transformed to corresponding substituted thienobenzo/naphtho-triazoles in high isolated yields. They were prepared to study the acetyl- and butyrylcholinesterase inhibition associated with the inhibition of TNFα cytokine production and anti-inflammatory activity. The best experimental results were achieved with the allyl-thienobenzotriazole and isopropyl, p-methoxybenzyl, and hydroxybutyl substituted naphthotriazoles bearing additional chloro or methoxy groups. The allyl-thienobenzotriazole photoproduct is twice as potent an inhibitor of eqBChE compared to the standard galantamine. At the same time, this compound strongly inhibited TNFα production in PBMCs in response to the LPS stimulus. The complexes between selected compounds with the active site of BChE and AChE are assessed by docking, providing insight into the stabilizing interactions between the potential inhibitor and the active site.

Keywords
1,2,3-triazolo(thieno)stilbenes; Anti-inflammatory activity; Cholinesterase inhibition; Molecular docking; Naphtho/thienobenzo-triazoles.