Peer-Reviewed Publication
Eur J Med Chem2026;315118984.October 5, 2026Journal Article
One destination, three routes: Tacrine-Celecoxib hybrids targeting cholinesterases, COX-2, and carbonic anhydrases in cognitive impairment linked to metabolic dysfunction.
Nayera W Hassan1, Ola S Afifi1, Maryam A Z El-Attar1, Yasmine N Kamel2, Hend A Yassin2, Hanan Mohamed Nomeir2, Andrea Angeli3, Hala F Labib4, Manal A Elsheikh5, Mariam Zewail5, Evelyn M Gerges6, Ahmed F El-Yazbi7, Rosaria Spagnuolo8, Marina Naldi8, Mohamed I Ashmawy9, Waheed K Zahra10, Sherif F Hammad11, Claudiu T Supuran12, Manuela Bartolini13, Perihan A Elzahhar14, Ahmed S F Belal15, Shrouk M Abd El Wahab16
1Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Alexandria University, Alexandria, 21521, Egypt.
2Department of Medical Biochemistry, Faculty of Medicine, Alexandria University, Alexandria, 21131, Egypt.
3NEUROFARBA Department, Section of Pharmaceutical and Nutraceutical Sciences, University of Florence, Polo Scientifico, Via U. Schiff 6, Sesto Fiorentino, Firenze, 50019, Italy.
4Department of Pharmaceutical Chemistry, College of Pharmacy, Arab Academy for Science, Technology and Maritime Transport, Alamein, Egypt.
5Department of Pharmaceutics, Faculty of Pharmacy, Damanhour University, Damanhour, 22511, Egypt.
6Department of Pharmacology and Toxicology, Faculty of Pharmacy, Alexandria University, Alexandria, 21521, Egypt.
7Department of Pharmacology and Toxicology, Faculty of Pharmacy, Alexandria University, Alexandria, 21521, Egypt; Faculty of Pharmacy and the Research & Innovation Hub, Alamein International University, Alamein, 51718, Egypt.
8Department of Pharmacy and Biotechnology, Alma Mater Studiorum, University of Bologna, Bologna, 40126, Italy.
9Biotechnology Department, Faculty of Basic and Applied Sciences, Egypt-Japan University of Science and Technology, New Borg El-Arab, Alexandria, 21934, Egypt.
10Department of Mathematics, Institute of Basic and Applied Sciences, Egypt-Japan University of Science and Technology (E-JUST), New Borg El-Arab, Alexandria, 21934, Egypt; Department of Engineering Physics and Mathematics, Faculty of Engineering, Tanta University, Tanta, 31527, Egypt.
11Pharmaceutical Chemistry Department, Faculty of Pharmacy, Capital University (Formerly Helwan University), Cairo, 11795, Egypt; Medicinal Chemistry Department, Faculty of Pharmacy, Egypt-Japan University of Science and Technology (E-JUST), New Borg El-Arab, Alexandria, 21934, Egypt.
12NEUROFARBA Department, Section of Pharmaceutical and Nutraceutical Sciences, University of Florence, Polo Scientifico, Via U. Schiff 6, Sesto Fiorentino, Firenze, 50019, Italy. Electronic address: claudiu.supuran@unifi.it.
13Department of Pharmacy and Biotechnology, Alma Mater Studiorum, University of Bologna, Bologna, 40126, Italy. Electronic address: manuela.bartolini3@unibo.it.
14Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Alexandria University, Alexandria, 21521, Egypt. Electronic address: perihan.elzahhar@alexu.edu.eg.
15Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Alexandria University, Alexandria, 21521, Egypt. Electronic address: ahmed.belal@alexu.edu.eg.
16Department of Pharmaceutical Chemistry, Faculty of Pharmacy, University of Damanhour, 22511, Egypt.
Abstract
In this study, a series of tacrine-celecoxib hybrid compounds was designed and synthesized to modulate key molecular targets implicated in metabolic dysfunction-associated mild cognitive impairment, including cyclooxygenase-2 (COX-2), carbonic anhydrases, and cholinesterases. Among the investigated derivatives, compound 10b was identified as the most balanced multitarget candidate, exhibiting sele…
Create a free account to keep reading
Free members get 10 full research views every month across publications, clinical trials, FDA clearances, adverse events, and NIH grants. No credit card required.
Want unlimited research access? See Pro plans