Exploring efficacy of indole-based dual inhibitors for α-glucosidase and α-amylase enzymes: In silico, biochemical and kinetic studies

• Published in: International journal of biological macromolecules 2020-07, Vol.154, p.217-232
• Main Authors: Kawde, Abdel-Nasser, Taha, Muhammad, Alansari, Raneem Saud, Almandil, Noor Barak, Anouar, El Hassane, Uddin, Nizam, Rahim, Fazal, Chigurupati, Sridevi, Nawaz, Muhammad, Hayat, Shawkat, Ibrahim, Mohamad, Elakurthy, Praveen Kumar, Vijayan, Venugopal, Morsy, Mohamed, Ibrahim, Hossieny, Baig, Nadeem, Khan, Khalid Mohammed
• Format: Article
• Language: English
• Subjects: alpha-Amylases - antagonists & inhibitors; alpha-Glucosidases - metabolism; Diabetes Mellitus, Type 2 - drug therapy; Enzymatic kinetic study; Glycoside Hydrolase Inhibitors - chemical synthesis; Glycoside Hydrolase Inhibitors - chemistry; Humans; Indole; Indoles - chemical synthesis; Indoles - chemistry; Kinetics; Molecular docking; Molecular Structure; Structure-Activity Relationship; α-Amylase; α-Glucosidase
• ISSN: 0141-8130; 1879-0003
• DOI: 10.1016/j.ijbiomac.2020.03.090

α-Glucosidase and α-amylase are enzymes which are associated with diabetic II. These enzymes break macromolecules of sugar into monosugar molecules which is soluble in body, hence increase the sugar level in blood. There is need to develop economical and save inhibitors to prevent them from breaking sugar macromolecules to soluble molecules which will control the level of sugar in blood. Therefore, we synthesized indole-based derivatives (1–18) and evaluated as dual inhibitor for α-glucosidase and α-amylase. These chemical scaffolds were built with variation in aryl ring which were found active with good to moderate activity for α-glucosidase having IC50 value ranging from 13.99 ± 0.10 to 59.09 ± 0.30 μM when compared with standard acarbose with IC50 of 11.29 ± 0.10 μM; for α-amylase IC50 value ranging from 13.14 ± 0.10 to 58.99 ± 0.30 μM when compared with the standard acarbose with IC50 of 11.12 ± 0.10 μM. Structure activity relationship (SAR) has been established for all compounds. Enzymatic kinetic study and molecular docking study have been carried out to investigate the binding interactions α-glucosidase and α-amylase enzyme. [Display omitted] •Studied in vitro α-glucosidase, α-amylase enzymes inhibition•Studied enzymatic kinetic of α-glucosidase, α-amylase inhibitors•Performed Molecular docking