Caterina Deruvo
OC16 – Caterina Deruvo
Università degli Studi di Bari “A. Moro” – Dipartimento di Farmacia – Scienze del Farmaco
| Investigation of novel guaiacol-bearing molecules as multi-targeted directed ligands (MTDLs) against Alzheimer’s disease-related targets |
| Deruvo Caterina1, Rosa Purgatorio1, Marianna Ranieri2, Modesto de Candia1, Marco Catto1, Orazio Nicolotti1, Grazia Tamma2, Cosimo D. Altomare1 1 Department of Pharmacy-Pharmaceutical Sciences, 2 Department of Biosciences Biotechnologies and Environment, University of Bari Aldo Moro, Via E. Orabona 4, 70125, Bari,Italy |
| Abstract Natural phenolic compounds such as eugenol, vanillin, curcumin and ferulic acid (FA) share a guaiacol fragment associated with antioxidant, anti-inflammatory, and neuroprotective activities, which make it a promising moiety of multitarget-directed ligands (MTDLs) for treating neurodegenerative disorders, including Alzheimer’s disease (AD) [1]. In this study, the guaiacyl moiety was conjugated with indole and isatine cores, as well as tetrahydroazepino-indoles and chromenopyridines previously disclosed by some of us as inhibitors of β-amyloid aggregation, cholinesterases and monoamine oxidases [2,3]. Herein, the activities toward the AD-related targets of the newly synthesized guaiacyl derivatives 2-5 were investigated and compared with the ferulic acid ethyl ester 1. The biological evaluation includes inhibition assays of acetylcholinesterase (AChE), butyrylcholinesterase (BChE), monoamine oxidases A and B (MAO A and B), β-amyloid aggregation studies, radical scavenging activity, and intracellular ROS measurements in cell models under oxidative stress conditions. |
| References [1] Li, D.; Rui, Y.; Guo, S.; Luan, F.; Liu, R.; Zeng, N. Ferulic acid: A review of its pharmacology, pharmacokinetics and derivatives. Life Sci. 2021, 284, 119921. https://doi.org/10.1016/j.lfs.2021.119921. [2] Purgatorio, R.; De Candia, M.; De Palma, A.; De Santis, F.; Pisani, L.; Campagna, F.; Cellamare, S.; Altomare, C. D.; Catto, M. Insights into Structure-Activity Relationships of 3-Arylhydrazonoindolin-2-One Derivatives for Their Multitarget Activity on β-Amyloid Aggregation and Neurotoxicity. Molecules 2018, 23 (7), 1544. https://doi.org/10.3390/molecules23071544. [3] Purgatorio, R.; Kulikova, L. N.; Pisani, L.; Catto, M.; De Candia, M.; Carrieri, A.; Cellamare, S.; De Palma, A.; Beloglazkin, A. A.; Reza Raesi, G.; Voskressensky, L. G.; Altomare, C. D. Scouting around 1,2,3,4‐Tetrahydrochromeno[3,2‐c]Pyridin‐10‐ones for Single‐ and Multitarget Ligands Directed towards Relevant Alzheimer’s Targets. ChemMedChem 2020, 15 (20), 1947–1955. https://doi.org/10.1002/cmdc.202000468. |