Exploring the Potential of Sulfonamide-Dihydropyridine Hybrids as Multitargeted Ligands for Alzheimer's Disease Treatment

被引：3
作者：
Dakhlaoui, Imen [1 ,2 ]
Bernard, Paul J. [1 ]
Pietrzak, Diana [3 ]
Simakov, Alexey [4 ]
Maj, Maciej [3 ]
Refouvelet, Bernard [1 ]
Beduneau, Arnaud [4 ]
Cornu, Raphael [4 ]
Jozwiak, Krzysztof [3 ]
Chabchoub, Fakher [2 ]
Iriepa, Isabel [5 ]
Martin, Helene [4 ]
Marco-Contelles, Jose [6 ]
Ismaili, Lhassane [1 ]
机构：
[1] Univ Franche Comte, Lab LINC, Pole Chim Med, UR 481, F-25000 Besancon, France
[2] Univ Sfax, Fac Sci Sfax, Lab Appl Chem, Heterocycles Lipids & Polymers, BP 802, Sfax 3000, Tunisia
[3] Med Univ Lublin, Dept Biopharm, Ul W Chodzki 4a, PL-20093 Lublin, Poland
[4] Univ Franche Comte, PEP EA4267, F-25000 Besancon, France
[5] Univ Alcala, Dept Organ Chem & Inorgan Chem, Km 33 6, Alcala De Henares 28871, Barcelona, Spain
[6] CSIC, Lab Med Chem IQOG, C-Juan Cierva 3, Madrid 28006, Spain
来源：
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES | 2023年 / 24卷 / 11期
关键词：
calcium channel antagonism; cholinesterase inhibition; Hantzsch reaction; multitarget directed ligands; Nrf2; OXIDATIVE STRESS; THERAPEUTIC TARGET; MELATONIN; NRF2; ANTIOXIDANT; INHIBITORS; PATHWAY; BUTYRYLCHOLINESTERASE; INFLAMMATION; HYPOTHESIS;
D O I：
10.3390/ijms24119742
中图分类号：
Q5 [生物化学]; Q7 [分子生物学];
学科分类号：
071010 ; 081704 ;
摘要：
Alzheimer's disease (AD) is a multifactorial neurodegenerative disease that has a heavy social and economic impact on all societies and for which there is still no cure. Multitarget-directed ligands (MTDLs) seem to be a promising therapeutic strategy for finding an effective treatment for this disease. For this purpose, new MTDLs were designed and synthesized in three steps by simple and cost-efficient procedures targeting calcium channel blockade, cholinesterase inhibition, and antioxidant activity. The biological and physicochemical results collected in this study allowed us the identification two sulfonamide-dihydropyridine hybrids showing simultaneous cholinesterase inhibition, calcium channel blockade, antioxidant capacity and Nrf2-ARE activating effect, that deserve to be further investigated for AD therapy.
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页数：17
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