Synthesis,characterization, molecular modeling,and potential antimicrobial and anticancer activities of novel 2-aminoisoindoline-1,3-dione derivatives |
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| Institution: | 1. Pharmacognosy and Pharmaceutical Chemistry Department, College of Pharmacy, Taibah University, P.O. Box 30039, Al-Madinha Al-Munawaraha 41477, Saudi Arabia;2. Pharmaceutical Organic Chemistry Department, Faculty of Pharmacy, Al-Azhar University, P.O. Box 11651, Cairo 11884, Egypt;3. Pharmaceutics and Pharmaceutical Technology Department, College of Pharmacy, Taibah University, P.O. Box 30039, Al-Madinha Al-Munawaraha 41477, Saudi Arabia;4. Department of Microbiology, Faculty of Pharmacy, Zagazig University, Zagazig 44519, Egypt;5. Department of Pharmaceutics, Faculty of Pharmacy, Helwan University, P.O. Box 11795, Cairo, Egypt;1. Institut de Chimie Moléculaire de Reims, UMR 7312-CNRS, Université de Reims Champagne-Ardenne, 51 rue Cognacq-Jay, 51096 Reims Cedex, France;2. INSERM U1247, Groupe de Recherche sur l’Alcool et les Pharmacodépendances (GRAP), Université de Picardie Jules Verne, C.U.R.S. (Centre Universitaire de Recherche en Santé), Chemin du Thil, 80000 Amiens, France;3. INSERM UMR-S 973, Molécules Thérapeutiques In Silico, Université de Paris Diderot, Sorbonne Paris Cité, 35 rue Hélène Brion, 75013 Paris Cedex, France;4. Structure Fédérative de Recherche-Champagne Ardenne Picardie Santé (SFR-CAP Santé), France;1. Chemistry Department, Faculty of Science, Fayoum University, Fayoum, Egypt;2. Central European Institute of Technology (CEITEC), Brno University of Technology, Purkyňova 464/118, 612 00 Brno, Czech Republic;3. Brno University of Technology, Faculty of Chemistry, Institute of Physical and Applied Chemistry, Purkyňova 464/118, 612 00 Brno, Czech Republic;4. Petrochemical Research Chair, Chemistry Department, College of Science, King Saud University, PO Box 2455, Riyadh 11451, Saudi Arabia;5. Chemistry Department, Faculty of Science, Ain Shams University, Cairo, Egypt;6. Textile Research Division, National Research Center, Dokki, PO Box 12622, Giza 12522, Egypt;1. M. I. Platov South-Russian State Polytechnic University, 346428 Novocherkassk, Russian Federation;2. A. N. Nesmeyanov Institute of Organoelement Compounds, Russian Academy of Sciences, 119991 Moscow, Russian Federation;1. Department of Pharmacy, Faculty of Biological Sciences, University of Malakand, Chakdara, 18000 Dir (L), KP, Pakistan;2. Department of Pharmaceutical Chemistry, College of Pharmacy, Najran University, Najran, Saudi Arabia;3. Department of Chemistry, COMSATS University Islamabad, Abbottabad Campus, 22060 Abbottabad, Pakistan;1. Department of Chemistry, Allama Iqbal Open University, Islamabad, Pakistan;2. Research Center for Modeling and Simulations, National University of Sciences and Technology, Islamabad, Pakistan;3. Department of Chemistry, Quaid-i-Azam University, Islamabad, Pakistan;4. Department of Biochemistry, Quaid-i-Azam University, Islamabad, Pakistan;1. School of Chemistry, The University of Manchester, Oxford Road, Manchester M13 9PL, United Kingdom;2. Manchester Institute of Biotechnology, The University of Manchester, 131 Princess Street, Manchester M1 7DN, United Kingdom;3. Natural and Medical Sciences Research Center, University of Nizwa, P.O Box 33, Postal Code 616, Birkat Al Mauz, Nizwa, Oman;4. Department of Chemistry, Quaid-i-Azam University-45320, Islamabad, Pakistan;5. Department of Chemistry, Abbottabad University of Science and Technology, Havelian, Abbottabad, Pakistan;6. Martin-Luther-University Halle-Wittenberg, Organic Chemistry, Kurt-Mothes-Str. 2, D-06120 Halle (Saale), Germany |
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| Abstract: | In an effort to establish new drug candidates with improved antimicrobial and anticancer activities, we report here synthesis, molecular modeling, and in vitro biological evaluation of novel substituted N-amino phthalamide derivatives (3a-b, 4a-b, 5a-j, and 6). Structures of the newly synthesized compounds were described by IR, 1H & 13CNMR and LC-MS spectral data. The novel compounds were evaluated for their antibacterial activity against four types of Gm+ve and two for Gm−ve types, and antifungal activity against three fungi microorganisms by well diffusion method. Of these novel compounds, Schiff bases showed mostly promising antibacterial activity compared to reference drugs. A successful step was done for explanation of their mode of action through molecular docking of most active molecules at DNA gyrase B enzyme and further were biologically tested. Moreover, the antiproliferative activity was tested against two human carcinoma cell lines (Human colon carcinoma (HCT-116) and human breast adenocarcinoma (MCF-7)) showing promising anticancer activity compared to doxorubicin drug. The data from structure-activity relationship (SAR) analysis revealed that the lypophilic properties of these compounds might be essential parameter for their activity and suggest that 2-amino phthalamide scaffold derivatives 5g and 5h exhibited good antimicrobial and anticancer activities and might used as leads for further optimization. |
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| Keywords: | 2-Aminoisoindoline-1 3-dione Sciff base Anticancer activity Structure-selectivity relationships |
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