title: Design, Synthesis and Evaluation of Novel Phthalimide Derivatives as in Vitro Anti-Microbial, Anti-Oxidant and Anti-Inflammatory Agents.
abstract: Sixteen new phthalimide derivatives were synthesized and evaluated for their in vitro anti-microbial, anti-oxidant and anti-inflammatory activities. The cytotoxicity for all synthesized compounds was also determined in cancer cell lines and in normal human cells. None of the target derivatives had any cytotoxic activity. (ZE)-2-[4-(1-Hydrazono-ethyl) phenyl]isoindoline-1,3-dione (12) showed remarkable anti-microbial activity. Its activity against Bacillus subtilis was 133%, 106% and 88.8% when compared with the standard antibiotics ampicillin, cefotaxime and gentamicin, respectively. Compound 12 also showed its highest activities in Gram negative bacteria against Pseudomonas aeruginosa where the percentage activities were 75% and 57.6% when compared sequentially with the standard antibiotics cefotaxime and gentamicin. It was also found that the compounds 2-[4-(4-ethyl-3-methyl-5-thioxo-1,2,4-triazolidin-3-yl)phenyl]isoindoline-1,3-dione (13b) and 2-[4-(3-methyl-5-thioxo-4-phenyl-1,2,4-triazolidin-3-yl)phenyl]isoindoline-1,3-dione (13c) had anti-oxidant activity. 4-(N'-{1-[4-(1,3-Dioxo-1,3-dihydro-isoindol-2-yl)-phenyl]-ethylidene}-hydrazino)-benzenesulfonamide (17c) showed the highest in vitro anti-inflammatory activity of the tested compounds (a decrease of 32%). To determine the mechanism of the anti-inflammatory activity of 17c, a docking study was carried out on the COX-2 enzyme. The results confirmed that 17c had a higher binding energy score (-17.89 kcal/mol) than that of the ligand celecoxib (-17.27 kcal/mol).
authors.affiliation: Department of Pharmaceutical Organic Chemistry, Faculty of Pharmacy, Beni Suef University, Beni Suef 62514, Egypt. feby.farag@yahoo.com.
authors.forename: Phoebe F
authors.initials: PF
authors.lastname: Lamie
authors.affiliation: Department of Pharmaceutical Organic Chemistry, Faculty of Pharmacy, Beni Suef University, Beni Suef 62514, Egypt. john_philoppes@yahoo.com.
authors.forename: John N
authors.initials: JN
authors.lastname: Phillopes
authors.affiliation: Department of Microbiology & Immunology, Faculty of Pharmacy, Beni Suef University, Beni Suef 62514, Egypt. dr.ahmed_micro@yahoo.com.
authors.forename: Ahmed O
authors.initials: AO
authors.lastname: El-Gendy
authors.affiliation: Laboratory of Growth Regulators & Department of Chemical Biology and Genetics, Centre of the Region Haná for Biotechnological and Agricultural Research, Institute of Experimental Botany ASCR & Palacký University, Šlechtitelů 27, 783 71 Olomouc, The Czech Republic. lucie.rarova@upol.cz.
authors.forename: Lucie
authors.initials: L
authors.lastname: Rarova
authors.affiliation: Laboratory of Growth Regulators & Department of Chemical Biology and Genetics, Centre of the Region Haná for Biotechnological and Agricultural Research, Institute of Experimental Botany ASCR & Palacký University, Šlechtitelů 27, 783 71 Olomouc, The Czech Republic. jiri.gruz@upol.cz.
authors.forename: Jiri
authors.initials: J
authors.lastname: Gruz
mesh_terms: D000890:Anti-Infective Agents / Q000138:chemical synthesis / Q000494:pharmacology*; D000893:Anti-Inflammatory Agents / Q000138:chemical synthesis / Q000494:pharmacology*; D000975:Antioxidants / Q000138:chemical synthesis / Q000494:pharmacology*; D001419:Bacteria / Q000187:drug effects*; D049109:Cell Proliferation / Q000187:drug effects; D015195:Drug Design; D061307:Human Umbilical Vein Endothelial Cells / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D066298:In Vitro Techniques; D008826:Microbial Sensitivity Tests; D008958:Models, Molecular; D016328:NF-kappa B / Q000378:metabolism; D009369:Neoplasms / Q000188:drug therapy / Q000473:pathology*; D010797:Phthalimides / Q000138:chemical synthesis / Q000494:pharmacology*; D017382:Reactive Oxygen Species / Q000378:metabolism; D014407:Tumor Cells, Cultured
chemical_list: D000890:Anti-Infective Agents; D000893:Anti-Inflammatory Agents; D000975:Antioxidants; D016328:NF-kappa B; D010797:Phthalimides; D017382:Reactive Oxygen Species
keywords: anti-inflammatory; anti-microbial; anti-oxidant; phthalimides; synthesis