Zinc enzymes in medicinal chemistry

Hou, Rui; He, Yan; Yan, Guangwei; Hou, Shuzeng; Xie, Zhouling; Liao, Chenzhong

doi:10.1016/j.ejmech.2021.113877

Cited by 26 publications

(17 citation statements)

References 102 publications

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“…Zinc is an essential trace element and its deficiency results in various pathologies or potentiates them [ 160 , 161 ]. Zinc ions are necessary for the activity of over three hundred enzymes in the human body [ 162 ]. Zinc compounds have a variety of positive effects on oral health but are not common in mouthwashes.…”

Section: Discussionmentioning

confidence: 99%

A Fresh Look at Mouthwashes—What Is Inside and What Is It For?

Radzki

Wilhelm-Węglarz

Pruska

et al. 2022

IJERPH

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Mouthwashes are a very popular additional oral hygiene element and there are plenty of individual products, whose compositions are in a state of flux. The aim of our study was to investigate the compositions of mouthwashes and their functions, as well as to discuss their effectiveness in preventing and curing oral diseases and side effects. We searched for mouthwashes available on the market in Poland. We identified 241 individual mouthwash products. The extraction of compositions was performed and functions of the ingredients were assessed. Then, analysis was performed. The evaluation revealed that there are plenty of ingredients, but a typical mouthwash is a water–glycerine mixture and consists of additional sweetener, surfactant, preservative, and some colourant and flavouring agent, as well as usually having two oral health substances, anticaries sodium fluoride and antimicrobial essential oils. The effectiveness or side effects of several substances of mouthwashes were thoroughly discussed. We recommend not multiplying individual mouthwash products and their ingredients beyond medical or pharmaceutical necessity, especially without scientific proof.

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Section: Discussionmentioning

confidence: 99%

A Fresh Look at Mouthwashes—What Is Inside and What Is It For?

Radzki

Wilhelm-Węglarz

Pruska

et al. 2022

IJERPH

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“…Multiple Food and Drug Association -approved drugs that target zinc-dependent metalloenzymes are recognized to be coordinated to the Zn 2+ ion cofactor through a zinc-binding group such as carboxylate, thiol, or hydroxamate, among others. 37 The Zn 2+ coordination in determining the basic pharmacological principles of ACE2 inhibition is also exemplified by the in crystallo binding mode of the potent inhibitor MLN-4760, previously published. 38 It is also worth noting that the partially negatively charged ether, and carbonyl oxygens of 1,8-cineole and citronellal, respectively, can accept a hydrogen bond from the nearby (<2.5 Å) polar residue Tyr-515 observed in the present study.…”

Section: Resultsmentioning

confidence: 95%

In vitro and in silico Evaluation of ACE2 and LOX Inhibitory Activity of Eucalyptus Essential Oils, 1,8-Cineole, and Citronellal

Sakallı

Teralı²,

Karadağ

et al. 2022

Natural Product Communications

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Eucalyptus essential oils are well-known and used especially in upper respiratory tract pathologies or diseases as herbal drug preparations. In the present study, the in vitro angiotensin-converting enzyme 2 (ACE2) and lipoxygenase (LOX) enzyme inhibitory potentials of commercial Eucalyptus globulus Labill. and Eucalyptus citriodora Hook. essential oils were evaluated for their potential anti-coronavirus disease 2019 (COVID-19), and anti-inflammatory effects. In addition, the major components, 1,8-cineole and citronellal, were evaluated for their ability to bind at the active site of either human ACE2 or human 5-LOX using an in silico setting. Before activity evaluation, Eucalyptus globulus and E citriodora essential oils were analysed by GC/FID and GC/MS, where 1,8-cineole (30%), and citronellal (80%) were identified as the major components, respectively. The in vitro ACE2 inhibition was calculated as 94.9% for E globulus, and that of E citriodora essential oil as 83.4%. In vitro LOX inhibition experiments for essential oils in the same order showed inhibitions of 71.3 and 91.4%, respectively, at 20 µg/mL test concentrations in microplate-based fluorometric assays. In addition, protein–ligand docking, and interaction profiling was used to gain structural and mechanistic insights into the in silico ACE2 and LOX inhibitory potentials of the major Eucalyptus essential oil constituents, 1,8-cineole as well as citronellal. The resulting data supported the in vitro findings; however, further in vivo studies are needed to confirm the activity.

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“…Histone deacetylase (HDAC) catalyzes the deacetylation of lysine residues in histone tails, resulting in chromatin condensation and then participating in transcriptional regulation, cell cycle control, and apoptosis. 137 Many hybrid HDAC inhibitors targeting HDACs and other targets, such as PARP, phosphoinositide 3-kinase (PI3K) and JAK, have been investigated to synergistically suppress tumor growth. 138 The CDK inhibitor alvocidib and the HDAC inhibitor vorinostat have been shown to synergize in leukemia, breast cancer, lung cancer, neuroblastoma, and esophageal cancer cells.…”

Section: Discovery and Development Of Cdk Inhibitorsmentioning

confidence: 99%

Lessons Learned from Past Cyclin-Dependent Kinase Drug Discovery Efforts

et al. 2022

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Inhibition of cyclin-dependent kinases (CDKs) has become an effective therapeutic strategy for treating various diseases, especially cancer. Over almost three decades, although great efforts have been made to discover CDK inhibitors, many of which have entered clinical trials, only four CDK inhibitors have been approved. In the process of CDK inhibitor development, many difficulties and misunderstandings have hampered their discovery and clinical applications, which mainly include inadequate understanding of the biological functions of CDKs, less attention paid to pan- and multi-CDK inhibitors, nonideal isoform selectivity of developed selective CDK inhibitors, overlooking the metabolic stability of early discovered CDK inhibitors, no effective resistance solutions, and a lack of available combination therapy and effective biomarkers for CDK therapies. After reviewing the mechanisms of CDKs and the research progress of CDK inhibitors, this perspective summarizes and discusses these difficulties or lessons, hoping to facilitate the successful discovery of more useful CDK inhibitors.

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Zinc enzymes in medicinal chemistry

Cited by 26 publications

References 102 publications

A Fresh Look at Mouthwashes—What Is Inside and What Is It For?

A Fresh Look at Mouthwashes—What Is Inside and What Is It For?

In vitro and in silico Evaluation of ACE2 and LOX Inhibitory Activity of Eucalyptus Essential Oils, 1,8-Cineole, and Citronellal

Lessons Learned from Past Cyclin-Dependent Kinase Drug Discovery Efforts

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