Modifications of flexible nonyl chain and nucleobase head group of (+)-erythro-9-(2′s-hydroxy-3′s-nonyl)adenine [(+)-EHNA] as adenosine deaminase inhibitors

Kandalkar, Sachin R.; Ramaiah, Parimi Atchuta; Joshi, Manoj Kumar; Wavhal, Atul; Waman, Yogesh; Raje, Amol A.; Tambe, Ashwini; Ansari, Shariq; De, Siddhartha; Palle, Venkata P.; Mookhtiar, Kasim A.; Deshpande, Anil M.; Barawkar, Dinesh A.

doi:10.1016/j.bmc.2017.09.015

Cited by 9 publications

(6 citation statements)

References 41 publications

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“…It is a semi-tight ADA inhibitor that at first step, represents a classical competitive inhibition, while later on a sequential rearrangement of the enzyme and inhibitor take place, yielding a tight ADA-inhibitor complex. [ 88 ] The erythro diastereomer is more active than the threo one and Ki value of EHNA ranges 1.6–7.0 nM, depending on the experimental conditions [ 61 ].…”

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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“…PAES, or structurally similar derivatives, may therefore be useful in the control of hypertension (Figure 1a) [68,69]. In addition, compounds containing an aminoethyl sulfide moiety have the ability to inhibit adenosine deaminase (ADA) (Figure 1b) [70], show β-adrenoreceptor blocking properties (Figure 1c) [71], and are used as inhibitors of DNA methyltransferases (Figure 1d) [72]. Commercially available tri-O-acetyl-D-glucal and tri-O-acetyl-D-galactal were deacetylated in the presence of sodium methanolate in methanol and produced D-glucal (1) and D-galactal (2) in quantitative yields [73].…”

Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Aziridine Ring Opening as Regio- and Stereoselective Access to C-Glycosyl-Aminoethyl Sulfide Derivatives

et al. 2022

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“…Deprotection under standard conditions employing TBAF afforded polyhydroxylated ketone 12 in 74 % yield. Equally efficient is the reduction of the keto group under Luche conditions which provided allyl alcohol derivative 13 . Transformation of the free alcohol functionality in 6c to form either ether 14 or ester 15 demonstrated the further potential for derivatization of this class of compounds.…”

Section: Resultsmentioning

confidence: 99%

“…(2R,3S,4R,E)‐1,3‐Bis(( tert ‐butyldimethylsilyl)oxy)‐6‐(naphthalen‐2‐yl)hex‐5‐ene‐2,4‐diol (13): To a stirred solution of ketone 6e (20 mg, 0.04 mmol) in methanol (2 mL) cerium chloride heptahydrate (11 mg, 0.044 mmol) was added and the mixture was cooled to ‐ 78 °C . To this suspension, sodium borohydride (1.7 mg, 0.044 mmol) in methanol (0.5 mL) was added in portions.…”

Section: Methodsmentioning

confidence: 99%

Stereocontrolled Synthesis of Highly Substituted trans α,β‐Unsaturated Ketones with Potent Anticancer Properties from Glycals

et al. 2019

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A novel synthetic route for highly substituted conjugated ketones has been developed utilizing glycals as starting materials. The two‐step process combined the Heck reaction/Lewis acid promoted ring opening to afford the products in 33–80 % overall yields and with a high level of trans stereoselectivity. Since the products are essentially the aldols, this methodology may be employed in some cases as an alternative synthetic route to the typical aldol condensation. Densely substituted, selectively protected conjugated ketones are synthetically attractive structures which, in our case, proved to be biologically equally appealing. Namely, they showed activity against several cancer cell lines, such as HeLa, K562, MDA‐MB‐453, in some instances overperforming cisplatin used as a standard.

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Modifications of flexible nonyl chain and nucleobase head group of (+)-erythro-9-(2′s-hydroxy-3′s-nonyl)adenine [(+)-EHNA] as adenosine deaminase inhibitors

Cited by 9 publications

References 41 publications

Therapeutic Perspectives of Adenosine Deaminase Inhibition in Cardiovascular Diseases

Therapeutic Perspectives of Adenosine Deaminase Inhibition in Cardiovascular Diseases

Aziridine Ring Opening as Regio- and Stereoselective Access to C-Glycosyl-Aminoethyl Sulfide Derivatives

Stereocontrolled Synthesis of Highly Substituted trans α,β‐Unsaturated Ketones with Potent Anticancer Properties from Glycals

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