Anti-HAV evaluation and molecular docking of newly synthesized 3-benzyl(phenethyl)benzo[g]quinazolines |
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| Institution: | 1. Department of Pharmaceutical Chemistry, College of Pharmacy, King Saud University, PO Box 2457, Riyadh 11451, Saudi Arabia;2. Department of Chemistry, College of Science and Humanities, Prince Sattam bin Abdulaziz University, PO Box 83, Al Kharj 11942, Saudi Arabia;3. Chemistry of Natural Products Group, Centre of Excellence for Advanced Sciences, National Research Centre, 33 El-Bohouth St. (Former El-Tahrir St.) Dokki, Cairo 12622, Egypt;1. Department of Pharmaceutics, UCL School of Pharmacy, University College London, London, United Kingdom;2. Centre for Pharmaceutical Studies, Laboratory of Pharmaceutical Science, Faculty of Pharmacy, University of Coimbra, Coimbra, Portugal;3. Chymiotechnon and Department of Chemistry, Faculty of Science and Technology, University of Coimbra, Coimbra, Portugal;1. Goethe-Universität, Frankfurt am Main, Germany;2. National Center for Global Health and Medicine, Chiba, Japan;3. Monash Health and Monash University, Melbourne, Australia;4. IRCCS Hospital ‘Casa Sollievo della Sofferenza’, San Giovanni Rotondo, Italy;5. Yonsei University College of Medicine, Seoul, Republic of Korea;6. Gilead Sciences, Inc., Foster City, CA, United States;7. University of Dundee, Dundee, United Kingdom;8. Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan;9. Icahn School of Medicine at Mount Sinai, New York, NY, United States;10. The Kirby Institute, University of New South Wales, Sydney, Australia;11. Johns Hopkins University School of Medicine, Baltimore, MD, United States;1. Department of Physiology and Developmental Biology, Brigham Young University, 4005 LSB, Provo, UT 84602, USA;2. Frost Biologic, Inc., 5201 South Green St., Suite 160, Salt Lake City, UT 84123, USA;1. CAS Key Laboratory of Chemistry of Northwestern Plant Resources and Key Laboratory for Natural Medicine of Gansu Province, Lanzhou Institute of Chemical Physics, Chinese Academy of Sciences (CAS), Lanzhou 730000, People’s Republic of China;2. Department of Drug Design and Pharmacology, University of Copenhagen, Universitetsparken 2, 2100 Copenhagen, Denmark;3. National Institute of Medicinal Materials, 3B Quang Trung, Hanoi, Viet Nam;4. Department of Pharmacy, Thai Binh Medical and Pharmacy University, 373 Ly Bon, Thai Binh, Viet Nam;1. Moscow Institute of Physics and Technology (State University), 9 Institutskiy lane, Dolgoprudny City, Moscow Region 141700, Russian Federation;2. Lomonosov Moscow State University, Chemistry Dept., Leninskie gory, Building 1/3, GSP-1, Moscow 119991, Russian Federation;3. National University of Science and Technology MISiS, 9 Leninskiy pr, Moscow 119049, Russian Federation;4. ChemDiv, San Diego, California, USA;5. Institute of Biochemistry and Genetics Ufa Science Centre Russian Academy of Sciences (IBG RAS), Oktyabrya Prospekt 71, 450054 Ufa, Russian Federation;6. Skolkovo Institute of Science and Technology, Skolkovo Innovation Center, Building 3, Moscow 143026, Russian Federation;7. Dmitry Mendeleev University of Chemical Technology of Russia, Miusskaya sq. 9, Moscow 125047, Russian Federation;8. Centaura LLC, Moscow, Russia;9. Lomonosov Moscow State University, Faculty of Bioengineering and Bioinformatics, Moscow, Russian Federation;11. Lomonosov Moscow State University, Faculty of Medicine, Moscow, Russian Federation |
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| Abstract: | Synthesized 3-benzyl(phenethyl)benzog]quinazolines (1–17) were evaluated in vitro to determine their effects against the anti-hepatitis A virus (HAV) using a cytopathic effect inhibition assay. Of the synthesized compounds, 16 and 17 showed considerably high anti-HAV activity, as indicated by their EC50 values of 27.59 and 18 μM, respectively, when compared to that of amantadine (37.3 μM), the standard therapeutic agent. In addition, they exhibited low cytotoxicity as indicated by their CC50 values, 290.63 and 569.45 μM, respectively. Compounds 1, 2, and 5 exhibited remarkable activity compared to the active compounds (16, 17) and amantadine. The selectivity index (SI) values were calculated and applied as a parameter for classifying the activity of the targets. In addition, molecular docking was performed to rationalize the SAR of the target compounds and analyze the binding modes between the docked-selected compounds and amino acid residues in the active site of the HAV-3C proteinase enzyme. |
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| Keywords: | Antiviral Benzoquinazolines Cytopathic effect Cytotoxicity Molecular docking 3C proteinase |
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