title: Evaluation of the thiazole Schiff bases as β-glucuronidase inhibitors and their in silico studies.
abstract: Twenty eight (28) derivatives 2-29 were synthesized and four analogs were found to exhibit single-digit IC(50) values as β-glucuronidase inhibitors. Molecular modeling indicates that three factors: substituent R, lone pair on the nitrogen of azomethine part, and the interactions made by the main skeleton of the molecule, determined the enzyme inhibitory potential of these compounds. The planar conformation of the molecules allows them to fit deep inside the pocket while blocking the entry of other physiological substrates seems to play an important role in their activity.
authors.affiliation: H. E. J. Research Institute of Chemistry, International Center for Chemical and Biological Sciences, University of Karachi, Karcahi , 75270, Pakistan, khalid.khan@iccs.edu.
authors.forename: Khalid Mohammed
authors.initials: KM
authors.lastname: Khan
authors.forename: Aneela
authors.initials: A
authors.lastname: Karim
authors.forename: Sumayya
authors.initials: S
authors.lastname: Saied
authors.forename: Nida
authors.initials: N
authors.lastname: Ambreen
authors.forename: Xayale
authors.initials: X
authors.lastname: Rustamova
authors.forename: Shagufta
authors.initials: S
authors.lastname: Naureen
authors.forename: Sajid
authors.initials: S
authors.lastname: Mansoor
authors.forename: Muhammad
authors.initials: M
authors.lastname: Ali
authors.forename: Shahnaz
authors.initials: S
authors.lastname: Perveen
authors.forename: M Iqbal
authors.initials: MI
authors.lastname: Choudhary
authors.forename: Guillermo Antonio
authors.initials: GA
authors.lastname: Morales
mesh_terms: D003198:Computer Simulation; D004791:Enzyme Inhibitors / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D005937:Glucaric Acid / Q000378:metabolism; D005966:Glucuronidase / Q000037:antagonists & inhibitors* / Q000378:metabolism; D020128:Inhibitory Concentration 50; D007783:Lactones / Q000378:metabolism; D008958:Models, Molecular; D008968:Molecular Conformation; D012545:Schiff Bases / Q000737:chemistry; D013844:Thiazoles / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*
chemical_list: C571832:D-Glucaric acid, 1,4-lactone; D004791:Enzyme Inhibitors; D007783:Lactones; D012545:Schiff Bases; D013844:Thiazoles; D005966:Glucuronidase; D005937:Glucaric Acid