2-Mercapto Benzothiazole Derivatives: As Potential Leads for the Diabetic Management.
Benzothiazoles
/ chemistry
Glycoside Hydrolase Inhibitors
/ chemical synthesis
Hypoglycemic Agents
/ chemistry
Kinetics
Models, Molecular
Molecular Docking Simulation
Protein Binding
Protein Conformation
Saccharomyces cerevisiae
/ enzymology
Structure-Activity Relationship
alpha-Glucosidases
/ chemistry
2-Mercapto benzothiazole
hyperglycemia
in silico studies. Type-II
diabetes mellitus
in vitro α-glucosidase inhibitory activity
insulin
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:
2020
2020
Historique:
received:
12
01
2019
revised:
07
05
2019
accepted:
17
05
2019
pubmed:
15
6
2019
medline:
4
5
2021
entrez:
15
6
2019
Statut:
ppublish
Résumé
Results of our previous studies on antiglycation activity, and the noncytotoxicity of 2-mercapto benzothiazoles, encouraged us to further widen our investigation towards the identification of leads against diabetes mellitus. 33 derivatives of 2-mercapto benzothiazoles 1-33 were evaluated for in vitro α- glucosidase inhibitory activity. Mode of inhibition was deduced by kinetic studies. To predict the interactions of 2-mercapto benzothiazole derivatives 1-33 with the binding pocket of α-glucosidase enzyme, molecular docking studies were performed on the selected inhibitors. Compounds 2-4, 6-7, 9-26, 28 and 30 showed many folds potent α-glucosidase inhibitory activity in the range of IC50 = 31.21-208.63 μM, as compared to the standard drug acarbose (IC50 = 875.75 ± 2.08 μM). It was important to note that except derivative 28, all other derivatives were also found previously to have antiglycating potential in the range of IC50 = 187.12-707.21 μM. A number of compounds were identified as dual nature as antiglycating agent and α- glucosidase inhibitors. These compounds may serve as potential lead candidates for the management of diabetes mellitus.
Sections du résumé
BACKGROUND
Results of our previous studies on antiglycation activity, and the noncytotoxicity of 2-mercapto benzothiazoles, encouraged us to further widen our investigation towards the identification of leads against diabetes mellitus.
METHODS
33 derivatives of 2-mercapto benzothiazoles 1-33 were evaluated for in vitro α- glucosidase inhibitory activity. Mode of inhibition was deduced by kinetic studies. To predict the interactions of 2-mercapto benzothiazole derivatives 1-33 with the binding pocket of α-glucosidase enzyme, molecular docking studies were performed on the selected inhibitors.
RESULTS
Compounds 2-4, 6-7, 9-26, 28 and 30 showed many folds potent α-glucosidase inhibitory activity in the range of IC50 = 31.21-208.63 μM, as compared to the standard drug acarbose (IC50 = 875.75 ± 2.08 μM). It was important to note that except derivative 28, all other derivatives were also found previously to have antiglycating potential in the range of IC50 = 187.12-707.21 μM.
CONCLUSION
A number of compounds were identified as dual nature as antiglycating agent and α- glucosidase inhibitors. These compounds may serve as potential lead candidates for the management of diabetes mellitus.
Identifiants
pubmed: 31195949
pii: MC-EPUB-98773
doi: 10.2174/1573406415666190612153150
doi:
Substances chimiques
Benzothiazoles
0
Glycoside Hydrolase Inhibitors
0
Hypoglycemic Agents
0
captax
5RLR54Z22K
alpha-Glucosidases
EC 3.2.1.20
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
826-840Informations de copyright
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