Synthesis and acetylcholinesterase enzyme inhibition properties of axially disubstituted silicon phthalocyanines and their quaternized derivatives

https://doi.org/10.1016/j.jorganchem.2022.122468Get rights and content

Highlights

  • Synthesis of axially disubstituted silicon phthalocyanines.

  • Synthesis of silicon phthalocyanines.

  • Investigation of acetylcholinesterase inhibition properties of silicon phthalocyanines.

Abstract

In this paper, axial 1,3-bis[4-(4-acetylpiperazin-1-yl)phenoxy]propanoxy and {2-[4-(4-acetylpiperazin-1-yl)phenoxy]ethoxy}ethoxy groups substituted silicon(IV) phthalocyanines (PP-D-Si, PP-OH2-Si) and their quaternized derivatives (PP-D-SiQ, PP-OH2-SiQ) were synthesized and characterized. The acetylcholinesterase inhibition values of 1,3-bis[4-(4-acetylpiperazin-1-yl)phenoxy]propanoxy and {2-[4-(4-acetylpiperazin-1-yl)phenoxy]ethoxy}ethoxy groups substituted silicon(IV) phthalocyanines (PP-D-Si, PP-OH2-Si) and their quaternized derivatives (PP-D-SiQ, PP-OH2-SiQ) were measured by IC50 that reduces enzyme activity to 50% refers to the concentration of inhibitor. The synthesis compounds were classified as silicon and their quaternized derivatives and tagged as PP-D-Si, PP-OH2-Si, PP-D-SiQ and PP-OH2-SiQ. Except for the result of PP-D-SiQ was 1.586 ± 0.129 µM, the results were expressed as mM ranged between 0.553 and 3.626 mM.

Introduction

Phthalocyanines are a class of pigments in organic chemistry. They have been investigated in many technological fields. They have an 18-π electron system and green-blue color [1]. Because of their strong chemical and physical properties, phthalocyanines have been intensively studied potential application in solar cells [2], [3], [4], catalysts [5,6], electrochemistry [7], [8], [9], electrochemical sensor [10,11], optical data storage [12,13], gas sensors [14,15], organic light-emitting diodes (OLEDs) [16,17], semiconductors [18], laser dyes [19], liquid crystals [20,21], photodynamic therapy (PDT) [22], [23], [24]. The disadvantage of phthalocyanines in these applications is low solubility. To overcome this problem, axially substituted phthalocyanines may be synthesized [25], [26], [27].

Alzheimer's disease (AD) is commonly cognize as a type of dementia, actually seen in elder people. Substantially, degeneration of cholinergic neurons which affects memory, consciousness, and behavior functions is recognized as the pathological hallmark of this disease [28,29]. Although many different compounds have been synthesized to find the correct target for AD healing, successful results have been obtained from very few of them. Moreover, the actual studies are still going on to discover the most effective ones which have the most capable of being a drug. During the treatment of this disease, it is expected that these synthesis compounds are acted as strong inhibitors effect on choline esterases such as acetylcholinesterase (AChE) and butyrylcholinesterase (BChE). These enzymes are responsible for catalyzing the hydrolysis of one of the neurotransmitters called acetylcholine (ACh) [30]. Especially, a decreasing tendency in the brain acetylcholine (ACh) levels is evaluated as a generally accepted hypothesis associated with the pathophysiology of cognitive dysfunction emerging in AD [31].

As a result of all these evaluations based on the scientific data, one of the effective ways to help increase ACh levels in the brain passes through cholinesterase inhibition. Therefore, in this current study, the four phthalocyanine structures were tested as a potential inhibitor of acetylcholinesterase (AChE), the obtaining results were compared with each other. In this study, synthesis and characterization of novel axially 1,3-bis[4-(4-acetylpiperazin-1-yl)phenoxy]propanoxy and {2-[4-(4-acetylpiperazin-1-yl)phenoxy]ethoxy}ethoxy groups substituted silicon(IV) phthalocyanines (PP-D-Si, PP-OH2-Si) and their quaternized derivatives (PP-D-SiQ, PP-OH2-SiQ) were reported for the first time. Their acetylcholinesterase inhibition properties were measured.

Section snippets

Materials and methods

The used materials, equipment and enzyme inhibition were supplied as supplementary information.

Synthesis and characterization

The synthetic procedure for the new axial 1,3-bis[4-(4-acetylpiperazin-1-yl)phenoxy]propanoxy and {2-[4-(4-acetylpiperazin-1-yl)phenoxy]ethoxy}ethoxy groups substituted silicon(IV) phthalocyanines (PP-D-Si, PP-OH2-Si) and their quaternized derivatives (PP-D-SiQ, PP-OH2-SiQ) is described in Figs. 1 and 2. PP-D-OH and PP-OH2 were obtained between 1-acetyl-4-(4-hydroxyphenyl)piperazine and 1-3-dibromo-2-propanol, 2-chloroethoxyethanol in DMF. The new silicon(IV) phthalocyanines PP-D-Si, PP-OH2-Si,

Conclusion

In conclusion, a series of some newly synthesized silicon phthalocyanines bearing 1,3-bis[4-(4-acetylpiperazin-1-yl)phenoxy]propanoxy and {2-[4-(4-acetylpiperazin-1-yl)phenoxy]ethoxy}ethoxy groups as axial (PP-D-Si, PP-OH2-Si) and their quaternized derivatives (PP-D-SiQ, PP-OH2-SiQ) were synthesized and determined in terms of their acetylcholinesterase inhibition activity. Except for one form among analyzed compounds, the data of PP-D-SiQ having of the best value can be seen as a prominent

Declaration of Competing Interest

The authors eppeared to influence the work reported in this paper.

Acknowledgment

This study was supported by The Research Fund of Karadeniz Technical University (Project no: 8762), Trabzon, Turkey.

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