Discovery of novel oxindole derivatives as potent α-glucosidase inhibitors.
A series of 6-chloro-3-oxindole derivatives 1-25 were synthesized in high yields by the reaction of 6-chlorooxindole with different aromatic aldehydes in the presence of piperidine. All the synthesized compounds were isolated with E configuration. The structures were confirmed using spectroscopic techniques, including (1)H NMR and EIMS. These compounds showed varying degree of yeast α-glucosidase inhibition and seven were found as potent inhibitors of the enzyme. Compounds 2, 3, 4, 5, 6, 23, and 25 exhibited IC50 values 2.71±0.007, 11.41±0.005, 37.93±0.002, 15.19±0.004, 24.71±0.007, 17.33±0.001, and 14.2±0.002μM, respectively, as compared to standard acarbose (IC50, 38.25±0.12μM). Docking studies helped to find interactions between the enzyme and the active compounds. As a result of this study, oxindoles have been discovered as a new class of α-glucosidase inhibitors which have not been reported earlier.
Department of Chemistry, Abdul Wali Khan University, Mardan 23200, Pakistan. Electronic address: mominkhan@awkum.edu.pk.
Momin
M
Khan
Department of Chemistry, Abdul Wali Khan University, Mardan 23200, Pakistan.
Muhammad
M
Yousaf
Department of Biochemistry, Abdul Wali Khan University, Mardan 23200, Pakistan.
Abdul
A
Wadood
Department of Biochemistry, Abdul Wali Khan University, Mardan 23200, Pakistan.
Muhammad
M
Junaid
Department of Biochemistry and Biotechnology, The Islamia University of Bahawalpur, Bahawalpur 63100, Pakistan.
Muhammad
M
Ashraf
Department of Biochemistry and Biotechnology, The Islamia University of Bahawalpur, Bahawalpur 63100, Pakistan.
Umber
U
Alam
Department of Chemistry, COMSATS Institute of Information Technology, University Road, Abbottabad 22060, Pakistan.
Muhammad
M
Ali
Department of Chemistry, COMSATS Institute of Information Technology, University Road, Abbottabad 22060, Pakistan.
Muhammad
M
Arshad
Department of Chemistry, Abdul Wali Khan University, Mardan 23200, Pakistan.
Zahid
Z
Hussain
H.E.J. Research Institute of Chemistry, International Center for Chemical and Biological Sciences, University of Karachi, Karachi 75270, Pakistan. Electronic address: hassaan2@super.net.pk.
Khalid Mohammed
KM
Khan
D004305:Dose-Response Relationship, Drug; D055808:Drug Discovery; D004791:Enzyme Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D006843:Hydrocarbons, Chlorinated / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D007211:Indoles / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D008958:Models, Molecular; D015394:Molecular Structure; D012441:Saccharomyces cerevisiae / Q000201:enzymology; D013329:Structure-Activity Relationship; D000520:alpha-Glucosidases / Q000378:metabolism*
D004791:Enzyme Inhibitors; D006843:Hydrocarbons, Chlorinated; D007211:Indoles; D000520:alpha-Glucosidases
Acarbose; Docking studies; Oxindole; α-Glucosidase