title: Synthesis of novel inhibitors of β-glucuronidase based on benzothiazole skeleton and study of their binding affinity by molecular docking.
abstract: Benzothiazole derivatives 1-26 have been synthesized and their in vitro β-glucuronidase potential has been evaluated. Compounds 4 (IC(50)=8.9 ± 0.25 μM), 5 (IC(50)=36.1 ± 1.80 μM), 8 (IC(50)=8.9 ± 0.38 μM), 13 (IC(50)=19.4 ± 1.00 μM), 16 (IC(50)=4.23 ± 0.054 μM), and 18 (IC(50)=2.26 ± 0.06 μM) showed β-glucuronidase activity potent than the standard (d-saccharic acid 1,4-lactone, IC(50)=48.4 ± 1.25 μM). Compound 9 (IC(50)=94.0 ± 4.16 μM) is found to be the least active among the series. All active analogs were also evaluated for cytotoxicity and none of the compounds showed any cytotoxic effect. Furthermore, molecular docking studies were performed using the gold 3.0 program to investigate the binding mode of benzothiazole derivatives. This study identifies a novel class of β-glucuronidase inhibitors.
authors.affiliation: HEJ Research Institute of Chemistry, International Center for Chemical and Biological Sciences, University of Karachi, Karachi 75270, Pakistan. hassaan2@super.net.pk
authors.forename: Khalid Mohammed
authors.initials: KM
authors.lastname: Khan
authors.forename: Fazal
authors.initials: F
authors.lastname: Rahim
authors.forename: Sobia Ahsan
authors.initials: SA
authors.lastname: Halim
authors.forename: Muhammad
authors.initials: M
authors.lastname: Taha
authors.forename: Momin
authors.initials: M
authors.lastname: Khan
authors.forename: Shahnaz
authors.initials: S
authors.lastname: Perveen
authors.lastname: Zaheer-Ul-Haq
authors.forename: Muhammad Ahmed
authors.initials: MA
authors.lastname: Mesaik
authors.forename: M
authors.initials: M
authors.lastname: Iqbal Choudhary
mesh_terms: D000818:Animals; D052160:Benzothiazoles / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D001665:Binding Sites / Q000187:drug effects; D002417:Cattle; D018360:Crystallography, X-Ray; D005966:Glucuronidase / Q000037:antagonists & inhibitors*; D006023:Glycoproteins / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D006801:Humans; D008099:Liver / Q000201:enzymology; D008958:Models, Molecular; D015394:Molecular Structure; D013237:Stereoisomerism; D013329:Structure-Activity Relationship
chemical_list: D052160:Benzothiazoles; D006023:Glycoproteins; C011473:beta-glucuronidase inhibitor; D005966:Glucuronidase; C005465:benzothiazole