Synthesis, in vitro β-glucuronidase inhibitory activity and in silico studies of novel (E)-4-Aryl-2-(2-(pyren-1-ylmethylene)hydrazinyl)thiazoles

• Published in: Bioorganic Chemistry
• Main Author: Salar U.; Khan K.M.; Syed S.; Taha M.; Ali F.; Ismail N.H.; Perveen S.; Wadood A.; Ghufran M.
• Format: Article
• Language: English
• Published: Academic Press Inc. 2017
• Online Access: https://www.scopus.com/inward/record.uri?eid=2-s2.0-85008692996&doi=10.1016%2fj.bioorg.2016.12.011&partnerID=40&md5=42292fa227465765af9d2f111fa1fbb6

Current research is based on the synthesis of novel (E)-4-aryl-2-(2-(pyren-1-ylmethylene)hydrazinyl)thiazole derivatives (3–15) by adopting two steps route. First step was the condensation between the pyrene-1-carbaldehyde (1) with the thiosemicarbazide to afford pyrene-1-thiosemicarbazone intermediate (2). While in second step, cyclization between the intermediate (2) and phenacyl bromide derivatives or 2-bromo ethyl acetate was carried out. Synthetic derivatives were structurally characterized by spectroscopic techniques such as EI-MS, 1H NMR and 13C NMR. Stereochemistry of the iminic double bond was confirmed by NOESY analysis. All pure compounds 2–15 were subjected for in vitro β-glucuronidase inhibitory activity. All molecules were exhibited excellent inhibition in the range of IC50 = 3.10 ± 0.10–40.10 ± 0.90 μM and found to be even more potent than the standard D-saccharic acid 1,4-lactone (IC50 = 48.38 ± 1.05 μM). Molecular docking studies were carried out to verify the structure-activity relationship. A good correlation was perceived between the docking study and biological evaluation of active compounds. © 2016 Elsevier Inc.