The effects of fluorine substitution on the chemical properties and inhibitory capacity of Donepezil anti-Alzheimer drug; density functional theory and molecular docking calculations

Khosravan, Azita; Marani, Safora; Googheri, Mohammad Sadegh Sadeghi

doi:10.1016/j.jmgm.2016.11.013

Cited by 13 publications

(6 citation statements)

References 23 publications

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“…Therefore, the exploration has never stopped for the role of fluorine in drug design since the first fluorinated drug (9α-fluoro-substituted corticosteroid fludrocortisone) was approved in the 1950s (Fried and Sabo 1954 ). Nowadays, fluorine functional groups are contained in more than 25–30% of drugs, such as mefloquine, teriflunomide, citalopram, sorafenib, efavirenz, tedizolid phosphate, donepezil, and vorapaxar (Adler et al 2019 ; Izquierdo et al 2019 ; Khosravan et al 2017 ; Markakis et al 2020 ; Mei et al 2019 , 2020b ; Palmer-Brown et al 2017 ; Zhang et al 2020b ).…”

Section: Applications Of Fluorinated Compoundsmentioning

confidence: 99%

“…Due to its non-polarizability, strong electrostatic interactions will be formed, resulting in attractiveness or repulsion (Yang et al 2015 ). Moreover, fluorine can change the p K a , affinity, dipole moment, stability, lipophilicity, and bioavailability of adjacent groups (Dos Santos et al 2020 ; Khosravan et al 2017 ; Muller et al 2007 ). Therefore, the target compounds doped with fluorine are endowed with stronger activity and stability, longer half-life, and better bioabsorbability (Moschner et al 2019 ; Ni and Hu 2016 ; Reichel and Karaghiosoff 2020 ), especially in the fields of pharmaceutical intermediates (Gillis et al 2015 ; Swallow 2015 ; Zhdankin et al 2017 ; Zou et al 2019 ), cancer treatment (Meanwell et al 2020 ), antiviral agents (Pomeisl et al 2019 ), photovoltaics, diagnostic probes and bioinspired materials (Moschner et al 2019 ).…”

Section: Introductionmentioning

confidence: 99%

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Enzymatic synthesis of fluorinated compounds

Cheng

2021

Appl Microbiol Biotechnol

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Fluorinated compounds are widely used in the fields of molecular imaging, pharmaceuticals, and materials. Fluorinated natural products in nature are rare, and the introduction of fluorine atoms into organic compound molecules can give these compounds new functions and make them have better performance. Therefore, the synthesis of fluorides has attracted more and more attention from biologists and chemists. Even so, achieving selective fluorination is still a huge challenge under mild conditions. In this review, the research progress of enzymatic synthesis of fluorinated compounds is summarized since 2015, including cytochrome P450 enzymes, aldolases, fluoroacetyl coenzyme A thioesterases, lipases, transaminases, reductive aminases, purine nucleoside phosphorylases, polyketide synthases, fluoroacetate dehalogenases, tyrosine phenol-lyases, glycosidases, fluorinases, and multienzyme system. Of all enzyme-catalyzed synthesis methods, the direct formation of the C-F bond by fluorinase is the most effective and promising method. The structure and catalytic mechanism of fluorinase are introduced to understand fluorobiochemistry. Furthermore, the distribution, applications, and future development trends of fluorinated compounds are also outlined. Hopefully, this review will help researchers to understand the significance of enzymatic methods for the synthesis of fluorinated compounds and find or create excellent fluoride synthase in future research. Key points • Fluorinated compounds are distributed in plants and microorganisms, and are used in imaging, medicine, materials science . • Enzyme catalysis is essential for the synthesis of fluorinated compounds . • The loop structure of fluorinase is the key to forming the C-F bond . Supplementary Information The online version contains supplementary material available at 10.1007/s00253-021-11608-0.

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Section: Applications Of Fluorinated Compoundsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Enzymatic synthesis of fluorinated compounds

Cheng

2021

Appl Microbiol Biotechnol

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“…Based on their analysis, acidic moieties like CF 3 , appeared to be the second most important substituent of these small organofluorine inhibitors implying fluorinated motifs as possible binding units to Aβ peptide. Khosravan et al [68] theoretically investigated the effect of fluorine substitution on an anti-Alzheimer drug donepezil (FDA approved), including seven fluorinated derivatives of it, via density functional theory (DFT) and molecular docking calculations. This study shows that the fluorine substitution influences the solubility, molecular polarity, and structural stability of the donepezil drug.…”

Section: The Role Of Fluorine-containing Compounds In the Modulation mentioning

confidence: 99%

Fluorinated Molecules and Nanotechnology: Future ‘Avengers’ against the Alzheimer’s Disease?

Dabur

Loureiro

Pereira

2020

IJMS

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Alzheimer’s disease (AD) is a serious health concern, affecting millions of people globally, which leads to cognitive impairment, dementia, and inevitable death. There is still no medically accepted treatment for AD. Developing therapeutic treatments for AD is an overwhelming challenge in the medicinal field, as the exact mechanics underlying its devastating symptoms is still not completely understood. Rather than the unknown mechanism of the disease, one of the limiting factors in developing new drugs for AD is the blood–brain barrier (BBB). A combination of nanotechnology with fluorinated molecules is proposed as a promising therapeutic treatment to meet the desired pharmacokinetic/physiochemical properties for crossing the BBB passage. This paper reviews the research conducted on fluorine-containing compounds and fluorinated nanoparticles (NPs) that have been designed and tested for the inhibition of amyloid-beta (Aβ) peptide aggregation. Additionally, this study summarizes fluorinated molecules and NPs as promising agents and further future work is encouraged to be effective for the treatment of AD.

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“…Wallin et al (2007) evaluated the results of three-year donepezil treatment and from their observation, the obtained results indicated a positive outcome in the routine clinical setting. To shed more light on donepezil derivatives as anti-Alzheimer's drugs, we selected 22 derivatives (Table 1; Figure 1) (Khosravan et al, 2017) and evaluated their cholinesterase enzymes (AChE and BuChE) inhibitory activity and amyloid-beta (Aβ) in silico (Yerdelen et al, 2015).…”

Section: Introductionmentioning

confidence: 99%

Theoretical Investigation of Some Donepezil-based Derivatives as Dual Inhibitors for beta-Amyloid- and Cholinesterase Enzymes

Meziane¹,

Ghomri²,

Bouchentouf³

et al. 2021

J Biochem Technol

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To treat Alzheimer's Disease (AD), which is the most prevalent form of dementia, cholinesterase enzymes (AChE and BuChE) and amyloid-beta (Aβ) are attractive targets. In this work, different computational approach namely Density Functional Theory (DFT), Molecular Docking, and multi-QSAR modeling were performed on 22 donepezil-based derivatives which were reported as potent dual Aβ and (AChE and BuChE) inhibitors. The molecular geometries of the studied derivatives were carried out using GAUSSIAN 09 software with the level of theory (DFT, 6/31g*). The dual inhibitors adopted minimum energy. The results pointed out the importance of the inhibitors' geometries in enzyme inhibition. The QSAR models elaborated by means of Molecular Operating Environment (MOE) package, showed good statistical values for targets AChE (R²adj = 0.976, q2 = 0.871, RMS = 0.130), BuChE (R²adj = 0.976, q2 = 0.554, RMS = 0.092) and Aβ (R²adj = 0.861, q2 = 0.525, RMS = 0.113). To identify the binding pattern between the ligands and target enzymes, we implemented molecular docking studies for the datasets. The obtained information was related to the essential structural features that were related to the QSAR of the predicted models.

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The effects of fluorine substitution on the chemical properties and inhibitory capacity of Donepezil anti-Alzheimer drug; density functional theory and molecular docking calculations

Cited by 13 publications

References 23 publications

Enzymatic synthesis of fluorinated compounds

Enzymatic synthesis of fluorinated compounds

Fluorinated Molecules and Nanotechnology: Future ‘Avengers’ against the Alzheimer’s Disease?

Theoretical Investigation of Some Donepezil-based Derivatives as Dual Inhibitors for beta-Amyloid- and Cholinesterase Enzymes

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