Adenosine deaminase inhibition

Bagheri, Seyed Reza; Saboury, Ali Akbar; Haertlé, Tomasz

doi:10.1016/j.ijbiomac.2019.09.078

Cited by 42 publications

(28 citation statements)

References 230 publications

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“…Typically, ADA inhibitors are classified into transition-state inhibitors, ground-state compounds and non-nucleoside inhibitors as shown in Table 1 [ 48 ]. The structure of transition-state inhibitors mimics that of the tetrahedral intermediate, which forms during the deamination process catalyzed by ADA.…”

Section: Inhibitors Of Ada Activitymentioning

confidence: 99%

Therapeutic Perspectives of Adenosine Deaminase Inhibition in Cardiovascular Diseases

et al. 2020

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Adenosine deaminase (ADA) is an enzyme of purine metabolism that irreversibly converts adenosine to inosine or 2′deoxyadenosine to 2′deoxyinosine. ADA is active both inside the cell and on the cell surface where it was found to interact with membrane proteins, such as CD26 and adenosine receptors, forming ecto-ADA (eADA). In addition to adenosine uptake, the activity of eADA is an essential mechanism that terminates adenosine signaling. This is particularly important in cardiovascular system, where adenosine protects against endothelial dysfunction, vascular inflammation, or thrombosis. Besides enzymatic function, ADA protein mediates cell-to-cell interactions involved in lymphocyte co-stimulation or endothelial activation. Furthermore, alteration in ADA activity was demonstrated in many cardiovascular pathologies such as atherosclerosis, myocardial ischemia-reperfusion injury, hypertension, thrombosis, or diabetes. Modulation of ADA activity could be an important therapeutic target. This work provides a systematic review of ADA activity and anchoring inhibitors as well as summarizes the perspectives of their therapeutic use in cardiovascular pathologies associated with increased activity of ADA.

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Section: Inhibitors Of Ada Activitymentioning

confidence: 99%

Therapeutic Perspectives of Adenosine Deaminase Inhibition in Cardiovascular Diseases

et al. 2020

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“…ADA2 is only present in eukaryotes and multicellular organisms. Unlike ADA1, ADA2 is not ubiquitous and coexists with ADA1 only in monocytes/macrophages, where it is involved in the immune defense 21 . ADA, known as a moonlighting protein, has multiple functions 22 .…”

Section: 3‐diazepine Derivatives As Enzyme Inhibitorsmentioning

confidence: 99%

“…ADA, known as a moonlighting protein, has multiple functions 22 . It can act as a catalyst, allosteric modulator, costimulator, cell‐cell communication molecule, and plays a central role in the development and upholding of the immune system development 21,23 . Despite numerous studies, the physiological role of ADA is actually not fully understood 24 …”

Section: 3‐diazepine Derivatives As Enzyme Inhibitorsmentioning

confidence: 99%

“…For several years, it has been proposed that inhibition of ADA may have a beneficial therapeutic effect in viral infections and in some types of lymphoproliferative disorders 21 . Thus, ADA inhibitors may modulate the immune response in lymphomas and increase the intensity of effect of purine analogues used in cancer chemotherapy and in antiviral treatments (e.g., fludarabin, cladribin or 3ʹ‐deoxyadenosine).…”

Section: 3‐diazepine Derivatives As Enzyme Inhibitorsmentioning

confidence: 99%

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1,3‐Diazepine: A privileged scaffold in medicinal chemistry

Malki

Martinez

Masurier

2021

Medicinal Research Reviews

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Privileged structures have been widely used as effective templates for drug discovery. While benzo‐1,4‐diazepine constitutes the first historical example of such a structure, the 1,3 analogue is just as rich in terms of applications in medicinal chemistry. The 1,3‐diazepine moiety is present in numerous biological active compounds including natural products, and is used to design compounds displaying a large range of biological activities. It is present in the clinically used anticancer compound pentostatin, in several recent FDA approved β‐lactamase inhibitors (e.g., avibactam) and also in coformycin, a natural product known as a ring‐expanded purine analogue displaying antiviral and anticancer activities. Several other 1,3‐diazepine containing compounds have entered into clinical trials. This heterocyclic structure has been and is still widely used in medicinal chemistry to design enzyme inhibitors, GPCR ligands, and so forth. This review endeavours to highlight the main use of the 1,3‐diazepine scaffold and its derivatives, and their applications in medicinal chemistry, drug design, and therapy. We will focus more particularly on the development of enzyme inhibitors incorporating this scaffold, with a strong emphasis on the molecular interactions involved in the inhibition mechanism.

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“…Adenosine deaminase (ADA) is a key enzyme in purine metabolism that catalyzes the irreversible conversion of adenosine and deoxyadenosine to inosine and deoxyinosine, respectively [ 1 , 2 ]. ADA is extensively expressed in various human tissues, with the highest activity in thymus, spleen and other lymphoid tissues, and is related to cell mediated immunity [ 3 , 4 ].…”

Section: Introductionmentioning

confidence: 99%

Inverse relationship between serum adenosine deaminase levels and islet beta cell function in patients with type 2 diabetes

Cao

Wang

et al. 2021

Diabetol Metab Syndr

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Objective Type 2 diabetes (T2D) is a chronic low-grade inflammatory disease, which characterized by islet beta cell dysfunction. Serum adenosine deaminase (ADA) is an important enzyme that regulates the biological activity of insulin, and its levels are greatly increased in inflammatory diseases with insulin resistance. The present study was designed to explore the relationship between serum ADA levels and islet beta cell function in patients with T2D. Methods This cross-sectional study recruited 1573 patients with T2D from the Endocrinology Department of the Affiliated Hospital 2 of Nantong University between 2015 and 2018. All participants were received serum ADA test and oral glucose tolerance test (OGTT). Insulin sensitivity index (assessed by Matsuda index using C-peptide, ISIM-cp), insulin secretion index (assessed by ratio of area under the C-peptide curve to glucose curve, AUCcp/glu) and islet beta cell function (assessed by insulin secretion-sensitivity index 2 using C-peptide, ISSI2cp) were derived from OGTT. And other clinical parameters, such as HbA1c, were also collected. Results It was showed that HbA1c was significantly increased, while ISIM-cp, AUCcp/glu and ISSI2cp significantly decreased, across ascending quartiles of serum ADA levels. Moreover, serum ADA levels were negatively correlated with ISSI2cp (r = − 0.267, p < 0.001). Furthermore, after adjusting for other clinical parameters by multiple linear regression analysis, serum ADA levels were still independently associated with ISSI2cp (β = − 0.125, t = − 5.397, p < 0.001, adjusted R2 = 0.459). Conclusions Serum ADA levels are independently associated with islet beta cell function in patients with T2D.

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Adenosine deaminase inhibition

Cited by 42 publications

References 230 publications

Therapeutic Perspectives of Adenosine Deaminase Inhibition in Cardiovascular Diseases

Therapeutic Perspectives of Adenosine Deaminase Inhibition in Cardiovascular Diseases

1,3‐Diazepine: A privileged scaffold in medicinal chemistry

Inverse relationship between serum adenosine deaminase levels and islet beta cell function in patients with type 2 diabetes

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