Design, synthesis and biological evaluation of 1,3-dihydroxyxanthone derivatives: Effective agents against acetylcholinesterase

Menéndez, Cintia A.; Biscussi, Brunella; Accordino, Sebastián R.; Murray, Ana Paula; Gerbino, Darío C.; Appignanesi, Gustavo A.

doi:10.1016/j.bioorg.2017.09.012

Cited by 14 publications

(8 citation statements)

References 35 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…[23] Especially, xanthone derivatives as cholinesterase inhibitors have received significant attention in the recent years. [24,25] In this work, four xanthone derivatives with tertiary amine side chains have been synthesized as novel effective candidates against AD. The rational design of these xanthone derivatives is shown in Scheme 1.…”

Section: Introductionmentioning

confidence: 99%

“…They display a wide range of biological activities, such as anti‐inflammatory, [19] antitumor, [20] antioxidant [21] and inhibition of cholinesterase, [22] which has led to the xanthones being designated as ′privileged structures’ [23] . Especially, xanthone derivatives as cholinesterase inhibitors have received significant attention in the recent years [24,25] …”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Design, Synthesis and Biological Evaluation of Xanthone Derivatives for Possible Treatment of Alzheimer's Disease Based on Multi‐Target Strategy

Yang

Qiao

Hui

et al. 2020

Chemistry & Biodiversity

View full text Add to dashboard Cite

Four xanthone derivatives were synthesized and evaluated as acetylcholinesterase inhibitors (AChEIs) with metal chelating ability and antioxidant ability against Alzheimer's disease (AD). Most of them exhibited potential acetylcholinesterase (AChE), butylcholinesterase (BuChE) inhibitory, antioxidant and metal chelating properties. Among them, 1-hydroxy-3-[2-(pyrrolidin-1-yl)ethoxy]-9H-xanthen-9-one had the highest ability to inhibit AChE and displayed high selectivity towards AChE (IC 50 = 2.403 � 0.002 μM for AChE and IC 50 = 31.221 � 0.002 μM for BuChE), and it was also a good antioxidant (IC 50 = 2.662 � 0.003 μM). Enzyme kinetic studies showed that this compound was a mixed-type inhibitor, which could interact simultaneously with the catalytic anionic site (CAS) and the peripheral anionic site (PAS) of AChE. Interestingly, its copper complex showed more significant inhibitory activity for AChE (IC 50 = 0.934 � 0.002 μM) and antioxidant activity (IC 50 = 1.064 � 0.003 μM). Molecular dockings were carried out for the four xanthone derivatives in order to further investigate the binding modes. Finally, the blood-brain barrier (BBB) penetration prediction indicated that all compounds might penetrate BBB. These results suggested that 1-hydroxy-3-[2-(pyrrolidin-1-yl)ethoxy]-9H-xanthen-9-one was promising AChEI with metal chelating ability and antioxidant ability for the further investigation.

show abstract

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Design, Synthesis and Biological Evaluation of Xanthone Derivatives for Possible Treatment of Alzheimer's Disease Based on Multi‐Target Strategy

Yang

Qiao

Hui

et al. 2020

Chemistry & Biodiversity

View full text Add to dashboard Cite

show abstract

“…Xanthones are a class of oxygen-containing heterocycles with γ-pyran moiety condensed with two benzene rings, which are widely distributed in nature. 18) In recent years, xanthone derivatives have been received considerable attention in the field of medicinal chemistry because of their diversely biological functions, 20,21) such as anti-oxidant, 22) anti-hypertensive, 23) anti-convulsant, 24) anti-cholinesterase, 25) anti-malarial, 26) antimicrobial, 27) anti-inflammatory, 28) and anti-cancer activities. 29) Besides, they also served as the effective inhibitors of several enzymes like α-glycosidase, 30,31) topoisomerase, 32) proteinkinase, 33) aromatase.…”

Section: Introductionmentioning

confidence: 99%

Study on Synthesis and Biological Evaluation of 3-Aryl Substituted Xanthone Derivatives as Novel and Potent Tyrosinase Inhibitors

Chen

Luo

et al. 2019

CHEMICAL & PHARMACEUTICAL BULLETIN

View full text Add to dashboard Cite

Tyrosinase plays a key role in the melanin biosynthesis since it catalyzes the transformation of tyrosine into L-dopaquinone. A large number of studies have also shown that molecules to efficiently inhibit the activity of tyrosinase would be potentially used in treating many depigmentation-related disorders. In this study, we targeted a series of structure-based 3-aryl substituted xanthone derivatives in which diverse functional groups were respectively attached on 3-aromatic ring moiety as new tyrosinase inhibitors. The results demonstrated that all obtained compounds had potent tyrosinase inhibitory activities with IC 50 values at micromolar range. Especially, compound 4t was found to be the most active tyrosinase inhibitor with the IC 50 value of 11.3 µM, uncovering that the introduction of the proper hydroxyl group in the 3-aromatic ring was beneficial for enhancing the inhibitory potency against tyrosinase. Moreover, the inhibition mechanism and inhibition kinetics studies revealed that compound 4t presented such inhibitory effect by acting as the reversible and competitive-uncompetitive mixed-II type inhibitor. Further molecular docking simulation showed that 3-aromatic ring of compound 4t was inserted into the narrow regions of binuclear copper-binding site at the bottom of the enzyme binding pocket, while the xanthone skeleton was positioned at the surface of tyrosinase. Taken together, these data suggested that such type of molecules might be utilized for the development of new and promising candidate for the treatment of depigmentation-related disorders.

show abstract

“…9,10 Substitution of phosphorus oxychloride-zinc chloride by phosphorus pentoxide-methanesulfonic acid (Eaton's reagent) as an acylation catalyst generally led to better results. 18,19,23,24,33,35,40,50,54,59,63,70,[106][107][108][109][110][111][112][113][114][115][116][117][118][119][120][121] Since both of these methodologies had previously been extensively reviewed, 9,10 they will not be discussed herein.…”

Section: Synthesis Of Xanthones By Condensation Of a Salicylic Acid Wmentioning

confidence: 99%

Recent advances in the synthesis of xanthones and azaxanthones

et al. 2020

View full text Add to dashboard Cite

show abstract

Design, synthesis and biological evaluation of 1,3-dihydroxyxanthone derivatives: Effective agents against acetylcholinesterase

Cited by 14 publications

References 35 publications

Design, Synthesis and Biological Evaluation of Xanthone Derivatives for Possible Treatment of Alzheimer's Disease Based on Multi‐Target Strategy

Design, Synthesis and Biological Evaluation of Xanthone Derivatives for Possible Treatment of Alzheimer's Disease Based on Multi‐Target Strategy

Study on Synthesis and Biological Evaluation of 3-Aryl Substituted Xanthone Derivatives as Novel and Potent Tyrosinase Inhibitors

Recent advances in the synthesis of xanthones and azaxanthones

Contact Info

Product

Resources

About