Acridine-based (thio)semicarbazones and hydrazones: Synthesis, in vitro urease inhibition, molecular docking and in-silico ADME evaluation.

Autor: Isaac IO; H. E. J. Research Institute of Chemistry, International Center for Chemical and Biological Sciences, University of Karachi, Karachi 75270, Pakistan., Al-Rashida M; Department of Chemistry, Forman Christian College (A Chartered University), Ferozepur Road, Lahore 54600, Pakistan., Rahman SU; Center for Advanced Drug Research, COMSATS Institute of Information Technology, Abbottabad 22060, Pakistan., Alharthy RD; Department of Chemistry, Science and Arts College, Rabigh Campus, King Abdulaziz University, Jeddah, Saudi Arabia., Asari A; School of Fundamental Science, Universiti Malaysia Terengganu, 21030 Kuala Nerus, Terengganu, Malaysia., Hameed A; H. E. J. Research Institute of Chemistry, International Center for Chemical and Biological Sciences, University of Karachi, Karachi 75270, Pakistan. Electronic address: abdul_hameed8@hotmail.com., Khan KM; H. E. J. Research Institute of Chemistry, International Center for Chemical and Biological Sciences, University of Karachi, Karachi 75270, Pakistan; Department of Clinical Pharmacy, Institute for Research and Medical Consultations (IRMC), Imam Abdulrahman Bin Faisal University, P.O. Box 31441, Dammam, Saudi Arabia., Iqbal J; Center for Advanced Drug Research, COMSATS Institute of Information Technology, Abbottabad 22060, Pakistan. Electronic address: drjamshed@ciit.net.pk.
Jazyk: angličtina
Zdroj: Bioorganic chemistry [Bioorg Chem] 2019 Feb; Vol. 82, pp. 6-16. Date of Electronic Publication: 2018 Sep 22.
DOI: 10.1016/j.bioorg.2018.09.032
Abstrakt: Urease is a bacterial enzyme that is responsible for virulence of various pathogenic bacteria such as Staphylococcus aureus, Proteus mirabilis, Klebsiella pneumoniae, Ureaplasma urealyticum, Helicobacter pylori and Mycobacterium tuberculosis. Increased urease activity aids in survival and colonization of pathogenic bacteria causing several disorders especially gastric ulceration. Hence, urease inhibitors are used for treatment of such diseases. In search of new molecules with better urease inhibitory activity, herein we report a series of acridine derived (thio)semicarbazones (4a-4e, 6a-6l) that were found to be active against urease enzyme. Molecular docking studies were carried out to better comprehend the preferential mode of binding of these compounds against urease enzyme. Docking against urease from pathogenic bacterium S. pasteurii was also carried out with favorable results. In silico ADME evaluation was done to determine drug likeness of synthesized compounds.
(Copyright © 2018 Elsevier Inc. All rights reserved.)
Databáze: MEDLINE
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