Novel diarylated tacrine derivatives: Synthesis, characterization, anticancer, antiepileptic, antibacterial, and antifungal activities

In this study, our goal was to synthesize novel aryl tacrine derivatives and assess their potential as anticancer, antibacterial agents, and enzyme inhibitors. We adopted a two‐step approach, initiating with the synthesis of dibromotacrine derivatives 3 and 4 through the Friedlander reaction. These...

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Bibliographic Details
Published in:Journal of biochemical and molecular toxicology 2024-04, Vol.38 (4), p.e23706-n/a
Main Authors: Mısır, Büşra A., Derin, Yavuz, Ökten, Salih, Aydın, Ali, Koçyiğit, Ümit M., Şahin, Hatice, Tutar, Ahmet
Format: Article
Language:English
Subjects:
5-Fluorouracil
Anti-Bacterial Agents - chemistry
Anti-Bacterial Agents - pharmacology
Antibacterial agents
anticancer agents
Anticancer properties
Anticonvulsants - pharmacology
Antifungal Agents - pharmacology
Antineoplastic Agents - chemistry
Cancer
Carbonic anhydrase
Chemical reactions
Cross coupling
Cytotoxicity
diarylated tacrine
enzyme inhibition
Enzyme inhibitors
Enzyme Inhibitors - pharmacology
Enzymes
Female
Fungicides
Humans
inducing apoptosis
Intermediates
Lung cancer
Microorganisms
Molecular Structure
Neoplasms
Pharmacology
Structure-Activity Relationship
Suzuki coupling
Synthesis
Tacrine
Tacrine - chemistry
Tacrine - pharmacology
Tumor cell lines
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Summary:In this study, our goal was to synthesize novel aryl tacrine derivatives and assess their potential as anticancer, antibacterial agents, and enzyme inhibitors. We adopted a two‐step approach, initiating with the synthesis of dibromotacrine derivatives 3 and 4 through the Friedlander reaction. These intermediates underwent further transformation into diarylated tacrine derivatives 3a–e and 4a–e using a Suzuki–Miyaura cross‐coupling reaction. Thorough characterization of these novel diarylated tacrines was achieved using various spectroscopic techniques. Our findings highlighted the potent anticancer effects of these innovative compounds across a range of cancer cell lines, including lung, gynecologic, bone, colon, and breast cancers, while demonstrating low cytotoxicity against normal cells. Notably, these compounds surpassed the control drug, 5‐Fluorouracil, in terms of antiproliferative activity in numerous cancer cell lines. Moreover, our investigation included an analysis of the inhibitory properties of these novel compounds against various microorganisms and cytosolic carbonic anhydrase enzymes. The results suggest their potential for further exploration as cancer‐specific, enzyme inhibitory, and antibacterial therapeutic agents. Notably, four compounds, namely, 5,7‐bis(4‐(methylthio)phenyl)tacrine (3d), 5,7‐bis(4‐(trifluoromethoxy)phenyl)tacrine (3e), 2,4‐bis(4‐(trifluoromethoxy)phenyl)‐7,8,9,10‐tetrahydro‐6H‐cyclohepta[b]quinolin‐11‐amine (4e), and 6,8‐dibromotacrine (3), emerged as the most promising candidates for preclinical studies. The novel aryl substituted tacrine were efficiently synthesized and their anticancer potentials were highlighted in this study. Their inducing apoptosis, cell migration, and mitochondrial membrane potentials were screened.
ISSN:1095-6670
1099-0461
DOI:10.1002/jbt.23706