Theophylline-based hybrids as acetylcholinesterase inhibitors endowed with anti-inflammatory activity: synthesis, bioevaluation, in silico and preliminary kinetic studies.

ABSTRACT: In this study, we investigated the conjugation of theophylline with different compounds of natural origin hoping to construct new hybrids with dual activity against cholinergic and inflammatory pathways as potential agents for the treatment of Alzheimer's disease (AD). Out of 28 tested hybrids, two hybrids, acefylline-eugenol 6d and acefylline-isatin 19, were able to inhibit acetylcholinesterase (AChE) at low micromolar concentration displaying IC₅₀ values of 1.8 and 3.3 μM, respectively, when compared to the galantamine standard AChE inhibitor. Moreover, the prepared hybrids exhibited a significant anti-inflammatory effect against lipopolysaccharide induced inflammation in RAW 264.7 and reduced nitric oxide (NO), tumor necrosis alpha (TNF-α), interleukin-1β (IL-1β), and interle

SUBMITTER: Elgazar AA 

PROVIDER: S-EPMC10463010 | biostudies-literature | 2023 Aug

REPOSITORIES: biostudies-literature