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.

引用

页数：17

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