Design, synthesis, and evaluation of novel bistrifluoromethyl‐based hydrazones as dual inhibitors of acetylcholinesterase and carbonic anhydrase enzymes for Alzheimer's disease

• Published in: Chemical biology & drug design Vol. 103; no. 2; pp. e14482 - n/a
• Main Authors: Dincel, Efe Doğukan, Başoğlu‐Ünal, Faika, Kuran, Ebru Didem, Kayra, Tülay, Aydın, Nurcan, Kanber, Esmanur, Gülçin, İlhami, Ulusoy‐Güzeldemirci, Nuray
• Format: Journal Article
• Language: English
• Published: England 01-02-2024
• Subjects: acetylcholinesterase; Acetylcholinesterase - metabolism; Alzheimer Disease - drug therapy; carbonic anhydrase; Carbonic Anhydrase Inhibitors; Carbonic Anhydrases - metabolism; Cholinesterase Inhibitors - chemistry; Humans; hydrazide‐hydrazone; Hydrazones - pharmacology; molecular docking; Molecular Structure; Structure-Activity Relationship; synthesis; synthesis; carbonic anhydrase; acetylcholinesterase; hydrazide-hydrazone; molecular docking
• ISSN: 1747-0277; 1747-0285
• DOI: 10.1111/cbdd.14482

In this project, non‐sulfonamide bistrifluoromethyl‐derived hydrazide‐hydrazones were synthesized as multi‐target‐directed ligands to treat Alzheimer's disease and then, the novel derivatives were characterized by diverse spectral methods. Acetylcholinesterase (AChE), and human carbonic anhydrase (hCA) inhibitory qualifications of these compounds were determined. The reported compounds (2a‐y) were determined to be effective inhibitors of the hCA I, hCA II and AChE enzymes with Ki values in the range of 1.130 ± 0.15–5.440 ± 0.93 μM for hCA I, 0.894 ± 0.05–6.647 ± 1.35 μM for hCA II, and 0.196 ± 0.03–4.222 ± 1.04 μM for AChE. In silico studies were also performed to illuminate the binding interactions.
Synthesis of 22 novel bistrufluoromethyl‐derived hydrazide hydrazones. AChE, hCA I, and hCA II activity evaluation. Compound displayed potent activities against AChE, hCAI, and hCAII.