title: Organocatalyzed Novel Synthetic Methodology for Highly Functionalized Piperidines as Potent α-Glucosidase Inhibitors.
abstract: An efficient atom-economic one-pot synthesis of highly functionalized piperidines was achieved by catalytic multicomponent reaction. A wide range of heterogeneous and homogenous catalysts were explored; however, promising results were achieved when a β-keto-ester was reacted with selected aromatic aldehydes and anilines by using N-acetyl glycine (NAG) as catalyst. The implication of this methodology is straightforward since the products were precipitated out from the reaction solution, eliminating the need of column chromatography purifications. The synthesized piperidines were screened against α-glucosidase inhibition, which revealed that these compounds were very active inhibitors, and some of the compounds showed even better inhibition than the reference compound, at low micromolar concentrations. In silico molecular modeling was also performed to investigate the binding modes of the compounds into the active sites of the target protein.
authors.affiliation: Interdisciplinary Research Center in Biomedical Materials (IRCBM), COMSATS Institute of Information Technology, Lahore, Pakistan.|Department of Chemistry, The Islamia University of Bahawalpur, Bahawalpur, Pakistan.
authors.forename: Ariba
authors.initials: A
authors.lastname: Farooq
authors.affiliation: Interdisciplinary Research Center in Biomedical Materials (IRCBM), COMSATS Institute of Information Technology, Lahore, Pakistan.
authors.forename: Lubna
authors.initials: L
authors.lastname: Shahazadi
authors.affiliation: Faculty of Pharmacy, Department of Physicochemical Drug Analysis, Jagiellonian University Medical College, Cracow, Poland.
authors.forename: Marek
authors.initials: M
authors.lastname: Bajda
authors.affiliation: Department of Chemistry, King Fahd University of Petroleum and Minerals, Dhahran, Saudi Arabia.
authors.forename: Nisar
authors.initials: N
authors.lastname: Ullah
authors.affiliation: Department of Chemistry, The Islamia University of Bahawalpur, Bahawalpur, Pakistan.
authors.forename: Abdul
authors.initials: A
authors.lastname: Rauf
authors.affiliation: Department of Chemistry, COMSATS Institute of Information Technology, Abbottabad, Pakistan.
authors.forename: Sohail Anjum
authors.initials: SA
authors.lastname: Shahzad
authors.affiliation: Interdisciplinary Research Center in Biomedical Materials (IRCBM), COMSATS Institute of Information Technology, Lahore, Pakistan.
authors.forename: Ather Farooq
authors.initials: AF
authors.lastname: Khan
authors.affiliation: Department of Biochemistry & Biotechnology, The Islamia University of Bahawalpur, Bahawalpur, Pakistan.
authors.forename: Muhammad
authors.initials: M
authors.lastname: Ashraf
authors.affiliation: Interdisciplinary Research Center in Biomedical Materials (IRCBM), COMSATS Institute of Information Technology, Lahore, Pakistan. drmyar@ciitlahore.edu.pk.
authors.forename: Muhammad
authors.initials: M
authors.lastname: Yar
mesh_terms: D055162:Biocatalysis / Q000187:drug effects; D060326:Chemistry Techniques, Synthetic / Q000379:methods*; D005998:Glycine / Q000031:analogs & derivatives / Q000737:chemistry; D065089:Glycoside Hydrolase Inhibitors / Q000138:chemical synthesis* / Q000494:pharmacology*; D008958:Models, Molecular; D010880:Piperidines / Q000138:chemical synthesis* / Q000494:pharmacology*; D013329:Structure-Activity Relationship; D000520:alpha-Glucosidases / Q000378:metabolism*
chemical_list: D065089:Glycoside Hydrolase Inhibitors; D010880:Piperidines; D000520:alpha-Glucosidases; D005998:Glycine; C006368:aceturic acid
keywords: 2,6-Substituted piperidines; Molecular modeling; N-acetyl glycine; Organocatalysis; α-Glucosidase