Autors: Violina T. Angelova., Borislav Georgiev., Tania Pencheva., Ilza Pajeva., Miroslav Rangelov., Nadezhda Todorova., Dimitrina Zheleva-Dimitrova., Yovkova, E. K., Iva V. Valkova., Nikolay Vassilev., Rositsa Mihaylova., Denitsa Stefanova., Boris Petrov., Yulian Voynikov., Virginia Tzankova.
Title: Design, Synthesis, In Silico Studies and In Vitro Evaluation of New Indole- and/or Donepezil-like Hybrids as Multitarget-Directed Agents for Alzheimer’s Disease
Keywords: AChE/BChE; Alzheimer’s disease; neuroprotection; SH-SY5Y;

Abstract: In this study, two novel series of melatonin- and donepezil-based hybrid molecules with hydrazone (3a–r) or sulfonyl hydrazone (5a–l) fragments were designed, synthesized, and evaluated as multifunctional ligands against AD-related neurodegenerative mechanisms. Two lead compounds (3c and 3d) exhibited a well-balanced multifunctional profile, demonstrating intriguing acetylcholinesterase (AChE) inhibition, promising antioxidant activity assessed by DPPH, ABTS, and FRAP methods, as well as the inhibition of lipid peroxidation in the linoleic acid system. Compound 3n, possessing two indole scaffolds, showed the highest activity against butyrylcholinesterase (BChE) and a high selectivity index (SI = 47.34), as well as a pronounced protective effect in H2O2-induced oxidative stress in SH-SY5Y cells. Moreover, compounds 3c, 3d, and 3n showed low neurotoxicity against malignant neuroblastoma cell lines of human (SH-SY5Y) and murine (Neuro-2a) origin,as well as normal murine fibroblast cells.

References

    Issue

    Journal of Pharmaceuticals, vol. 16, issue 9, pp. 1194, 2023, Sweden, MDPI, https://doi.org/10.3390/ph16091194

    Цитирания (Citation/s):
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    Вид: статия в списание, публикация в издание с импакт фактор, публикация в реферирано издание, индексирана в Scopus