Tetrahydroacridine derivatives with dichloronicotinic acid moiety as attractive, multipotent agents for Alzheimer's disease treatment

Czarnecka, Kamila; Chufarova, Nina V.; Halczuk, Krzysztof; Maciejewska, Karolina; Girek, Małgorzata; Skibiński, Robert; Jończyk, Jakub; Bajda, Marek; Kabziński, Jacek; Majsterek, Ireneusz; Szymański, Paweł

doi:10.1016/j.ejmech.2018.01.014

Cited by 23 publications

(7 citation statements)

References 30 publications

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“…To overcome the toxicity of tacrine, many efforts were made after its withdrawal from the market to decrease its side effects and to synthesize its new derivatives. Most of these novel tacrine-based compounds showed beneficial activities both in vitro and in vivo, and their high efficiency demonstrated that tacrine scaffold is an ideal starting point for designing and achieving potent and selective AChE’s ligands [ 15 , 16 , 17 ]. Tacrine and its analogues labelled with diagnostic radionuclide were also studied from point of view of their application as a potential diagnostic agent capable of determining AChE levels.…”

Section: Introductionmentioning

confidence: 99%

New Imaging Modality of COVID-19 Pneumonia Developed on the Basis of Alzheimer’s Disease Research

Koźmiński

Niedziałek

Wieczorek

et al. 2022

IJMS

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Viral pneumonia caused by highly infectious SARS-CoV-2 poses a higher risk to older people and those who have underlying health conditions, including Alzheimer’s disease. In this work we present newly designed tacrine-based radioconjugates with physicochemical and biological properties that are crucial for the potential application as diagnostic radiopharmaceuticals. A set of ten tacrine derivatives was synthesized, labelled with gallium-68 and fully characterized in the context of their physicochemical properties. Based on these results, the final two most promising radioconjugates, [68Ga]Ga-NODAGA-Bn-NH(CH2)9Tac and [68Ga]Ga-THP-NH(CH2)9Tac, were selected for biodistribution studies. The latter compound was proven to be a good inhibitor of cholinesterases with significant affinity toward the lungs, according to the biodistribution studies. On the basis of molecular modelling combined with in vitro studies, we unraveled which structural properties of the developed tacrine derivatives are crucial for high affinity toward acetylcholinesterase, whose increased levels in lung tissues in the course of coronavirus disease indicate the onset of pneumonia. The radiopharmaceutical [68Ga]Ga-THP-NH(CH2)9Tac was ultimately selected due to its increased accuracy and improved sensitivity in PET imaging of lung tissue with high levels of acetylcholinesterase, and it may become a novel potential diagnostic modality for the determination of lung perfusion, including in inflammation after COVID-19.

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Section: Introductionmentioning

confidence: 99%

New Imaging Modality of COVID-19 Pneumonia Developed on the Basis of Alzheimer’s Disease Research

Koźmiński

Niedziałek

Wieczorek

et al. 2022

IJMS

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“…Tetrahydroacridine, containing a partially hydrogenated ring, is another privileged scaffold which showed interesting biological activities [48][49][50][51][52][53][54]. As a typical example, 9-amino-1,2,3,4tetrahydroacridine or tacrine was the first drug approved for the treatment of Alzheimer's disease [55][56][57].…”

Section: Introductionmentioning

confidence: 99%

2,4-Bis(arylethynyl)-9-chloro-5,6,7,8-tetrahydroacridines: synthesis and photophysical properties

Tka¹,

Ayed²,

Braiek³

et al. 2021

Beilstein J. Org. Chem.

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Acridine derivatives have attracted considerable interest in numerous areas owing to their attractive physical and chemical properties. Herein, starting from readily available anthranilic acid, an efficient synthesis of 2,4-bis(arylethynyl)-9-chloro-5,6,7,8-tetrahydroacridine derivatives was accomplished via a one-pot double Sonogashira cross-coupling method. The UV-visible absorption and emission properties of the synthesized molecules have been examined. Additionally, theoretical studies based on density functional theory (DFT/B3LYP/6-31G(d)) were carried out.

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“…On the other hand, tetrahydroacridines have received much attention in medicinal chemistry, due to their ability to inhibit topoisomerase enzymes and block the DNA transcription [44,45]. In particular, they have been widely explored for the treatment of Alzheimer's disease [46][47][48][49][50][51], human cancer [52,53], and tuberculosis [54] (Figure 1).…”

Section: Introductionmentioning

confidence: 99%

Synthesis and investigation on optical and electrochemical properties of 2,4-diaryl-9-chloro-5,6,7,8-tetrahydroacridines

Tka¹,

Ayed²,

Braiek³

et al. 2021

Beilstein J. Org. Chem.

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A facile synthesis of 2,4-diaryl-9-chloro-5,6,7,8-tetrahydroacridine derivatives is reported which is based on POCl3-mediated cyclodehydration followed by double Suzuki–Miyaura cross-coupling. The absorption and fluorescence properties of the obtained products were investigated and their HOMO/LUMO energy levels were estimated by cyclic voltammetry measurements. Besides, density functional theory calculations were carried out for further exploration of their electronic properties.

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Tetrahydroacridine derivatives with dichloronicotinic acid moiety as attractive, multipotent agents for Alzheimer's disease treatment

Cited by 23 publications

References 30 publications

New Imaging Modality of COVID-19 Pneumonia Developed on the Basis of Alzheimer’s Disease Research

New Imaging Modality of COVID-19 Pneumonia Developed on the Basis of Alzheimer’s Disease Research

2,4-Bis(arylethynyl)-9-chloro-5,6,7,8-tetrahydroacridines: synthesis and photophysical properties

Synthesis and investigation on optical and electrochemical properties of 2,4-diaryl-9-chloro-5,6,7,8-tetrahydroacridines

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