Synthesis, in vitro α-glucosidase inhibitory activity and molecular docking studies of new thiazole derivatives.
Current study based on the synthesis of new thiazole derivatives via "one pot" multicomponent reaction, evaluation of their in vitro α-glucosidase inhibitory activities, and in silico studies. All synthetic compounds were fully characterized by (1)H NMR, (13)C NMR and EIMS. CHN analysis was also performed. These newly synthesized compounds showed activities in the range of IC50=9.06±0.10-82.50±1.70μM as compared to standard acarbose (IC50=38.25±0.12μM). It is worth mentioning that most of the compounds such as 1 (IC50=23.60±0.39μM), 2 (IC50=22.70±0.60μM), 3 (IC50=22.40±0.32μM), 4 (IC50=26.5±0.40μM), 6 (IC50=34.60±0.60μM), 7 (IC50=26.20±0.43μM), 8 (IC50=14.06±0.18μM), 9 (IC50=17.60±0.28μM), 10 (IC50=27.16±0.41μM), 11 (IC50=19.16±0.19μM), 12 (IC50=9.06±0.10μM), 13 (IC50=12.80±0.21μM), 14 (IC50=11.94±0.18μM), 15 (IC50=16.90±0.20μM), 16 (IC50=12.60±0.14μM), 17 (IC50=16.30±0.29μM), and 18 (IC50=32.60±0.61μM) exhibited potent inhibitory potential. Molecular docking study was performed in order to understand the molecular interactions between the molecule and enzyme. Newly identified α-glucosidase inhibitors except few were found to be completely non-toxic.
H. E. J. Research Institute of Chemistry, International Center for Chemical and Biological Sciences, University of Karachi, Karachi 75270, Pakistan. Electronic address: khalid.khan@iccs.edu.
Khalid Mohammed
KM
Khan
H. E. J. Research Institute of Chemistry, International Center for Chemical and Biological Sciences, University of Karachi, Karachi 75270, Pakistan.
Saira
S
Qurban
H. E. J. Research Institute of Chemistry, International Center for Chemical and Biological Sciences, University of Karachi, Karachi 75270, Pakistan.
Uzma
U
Salar
Atta-ur-Rahman Institute for Natural Product Discovery, Universiti Teknologi MARA (UiTM), Puncak Alam Campus, 42300 Bandar Puncak Alam, Selangor D. E., Malaysia; Faculty of Applied Science, Universiti Teknologi MARA, Shah Alam 40450, Selangor D. E., Malaysia.
Muhammad
M
Taha
H. E. J. Research Institute of Chemistry, International Center for Chemical and Biological Sciences, University of Karachi, Karachi 75270, Pakistan; Department of Chemistry, Karakoram International University Gilgit, Pakistan.
Shafqat
S
Hussain
PCSIR Laboratories Complex, Karachi, Shahrah-e-Dr. Salimuzzaman Siddiqui, Karachi 75280, Pakistan.
Shahnaz
S
Perveen
H. E. J. Research Institute of Chemistry, International Center for Chemical and Biological Sciences, University of Karachi, Karachi 75270, Pakistan.
Abdul
A
Hameed
Faculty of Applied Science, Universiti Teknologi MARA, Shah Alam 40450, Selangor D. E., Malaysia; Department of Chemistry, Karakoram International University Gilgit, Pakistan.
Nor Hadiani
NH
Ismail
Department of Biochemistry, Computational Medicinal Chemistry Laboratory, UCSS, Abdul Wali Khan University Mardan, Pakistan.
Muhammad
M
Riaz
Department of Biochemistry, Computational Medicinal Chemistry Laboratory, UCSS, Abdul Wali Khan University Mardan, Pakistan.
Abdul
A
Wadood
D016475:3T3 Cells; D000818:Animals; D002470:Cell Survival / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D065089:Glycoside Hydrolase Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D006801:Humans; D051379:Mice; D062105:Molecular Docking Simulation; D015394:Molecular Structure; D013329:Structure-Activity Relationship; D013844:Thiazoles / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D000520:alpha-Glucosidases / Q000378:metabolism*
D065089:Glycoside Hydrolase Inhibitors; D013844:Thiazoles; D000520:alpha-Glucosidases
In silico study; In vitro α-glucosidase; Structure-activity relationship; Synthesis; Thiazole