Chalcones as Scavengers of HOCl and Inhibitors of Oxidative Burst: Structure-Activity Relationship Studies.
Chalcones
antioxidant activity.
human neutrophils
hypochlorous acid
reactive species
scavenging activity
Journal
Medicinal chemistry (Shariqah (United Arab Emirates))
ISSN: 1875-6638
Titre abrégé: Med Chem
Pays: Netherlands
ID NLM: 101240303
Informations de publication
Date de publication:
2022
2022
Historique:
received:
01
07
2020
revised:
14
09
2020
accepted:
05
10
2020
pubmed:
1
1
2021
medline:
20
1
2022
entrez:
31
12
2020
Statut:
ppublish
Résumé
This study evaluates the ability of chalcones to scavenge hypochlorous acid (HOCl) and modulate oxidative burst. The chemistry of chalcones has long been a matter of interest to the scientific community due to the phenolic groups often present and to the various replaceable hydrogens that allow the formation of a broad number of derivatives. Due to this chemical diversity, several biological activities have been attributed to chalcones, namely anti-diabetic, anti-inflammatory and antioxidant. Evaluate the ability of a panel of 34 structurally related chalcones to scavenge HOCl and/or suppress its production through the inhibition of human neutrophils' oxidative burst, followed by the establishment of the respective structure-activity relationships. The ability of chalcones to scavenge HOCl was evaluated by fluorimetric detection of the inhibition of dihydrorhodamine 123 oxidation. The ability of chalcones to inhibit neutrophils' oxidative burst was evaluated by chemiluminometric detection of the inhibition of luminol oxidation. It was observed that the ability to scavenge HOCl depends on the position and number of hydroxy groups on both aromatic rings. Chalcone 5b was the most active with an IC50 value of 1.0 ± 0.1 μM. The ability to inhibit neutrophils' oxidative burst depends on the presence of a 2'-hydroxy group on A-ring and on other substituents groups, e.g. methoxy, hydroxy, nitro and/or chlorine atom( s) at C-2, C-3 and/or C-4 on B-ring, as in chalcones 2d, 2f, 2j, 2i, 4b, 2n and 1d, which were the most actives with IC50 values ranging from 0.61 ± 0.02 μM to 1.7 ± 0.2 μM. The studied chalcones showed high activity at a low micromolar range, indicating their potential as antioxidant agents and to be used as a molecular structural scaffold for the design of new anti-inflammatory compounds.
Sections du résumé
AIMS
OBJECTIVE
This study evaluates the ability of chalcones to scavenge hypochlorous acid (HOCl) and modulate oxidative burst.
BACKGROUND
BACKGROUND
The chemistry of chalcones has long been a matter of interest to the scientific community due to the phenolic groups often present and to the various replaceable hydrogens that allow the formation of a broad number of derivatives. Due to this chemical diversity, several biological activities have been attributed to chalcones, namely anti-diabetic, anti-inflammatory and antioxidant.
OBJECTIVES
OBJECTIVE
Evaluate the ability of a panel of 34 structurally related chalcones to scavenge HOCl and/or suppress its production through the inhibition of human neutrophils' oxidative burst, followed by the establishment of the respective structure-activity relationships.
METHODS
METHODS
The ability of chalcones to scavenge HOCl was evaluated by fluorimetric detection of the inhibition of dihydrorhodamine 123 oxidation. The ability of chalcones to inhibit neutrophils' oxidative burst was evaluated by chemiluminometric detection of the inhibition of luminol oxidation.
RESULTS
RESULTS
It was observed that the ability to scavenge HOCl depends on the position and number of hydroxy groups on both aromatic rings. Chalcone 5b was the most active with an IC50 value of 1.0 ± 0.1 μM. The ability to inhibit neutrophils' oxidative burst depends on the presence of a 2'-hydroxy group on A-ring and on other substituents groups, e.g. methoxy, hydroxy, nitro and/or chlorine atom( s) at C-2, C-3 and/or C-4 on B-ring, as in chalcones 2d, 2f, 2j, 2i, 4b, 2n and 1d, which were the most actives with IC50 values ranging from 0.61 ± 0.02 μM to 1.7 ± 0.2 μM.
CONCLUSION
CONCLUSIONS
The studied chalcones showed high activity at a low micromolar range, indicating their potential as antioxidant agents and to be used as a molecular structural scaffold for the design of new anti-inflammatory compounds.
Identifiants
pubmed: 33380306
pii: MC-EPUB-112813
doi: 10.2174/1573406417666201230093207
doi:
Substances chimiques
Chalcones
0
Chalcone
5S5A2Q39HX
Hypochlorous Acid
712K4CDC10
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
88-96Subventions
Organisme : European Union FEDER
ID : POCI-01-0145-FEDER-029253
Organisme : FCT, Fundação para a Ciência e Tecnologia
ID : PTDC/MEDQUI/29253/2017
Informations de copyright
Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.