title: Novel N-substituted indole Schiff bases as dual inhibitors of cyclooxygenase-2 and 5-lipoxygenase enzymes: Synthesis, biological activities in vitro and docking study.
abstract: Two new series of N-substituted indole derivatives 4a-l and 5a-h were synthesized. Their chemical structures were confirmed using spectroscopic tools including IR, (1)H NMR, (13)C NMR mass spectroscopy and elemental analyses. The results showed no significant cytotoxic activity on either cancer or normal human cells. Anti-inflammatory activity for all target compounds was evaluated in vitro. Compounds 5a-h were found to have better anti-inflammatory activity than 4a-l. The inhibitory activity of COX-2 and 5-LOX were tested for 5a-h. Three compounds, 5c, 5d and 5f showed excellent COX-2 inhibitory activity with IC50 ranging from 0.98 to 1.23 μM compared to the reference celecoxib (1.54 μM). These compounds had a reasonable selectivity index between 7.03 and 8.05. Additionally, p-methylbenzoyl derivative 5g (IC50 = 5.78 μM) had superior 5-LOX inhibitory activity, higher than quercetin. 5e was close to quercetin in its LOX inhibitory activity. Compounds 5a-h were docked inside the active site of COX-2 and 5-LOX enzymes.
authors.affiliation: Department of Pharmaceutical Organic Chemistry, Faculty of Pharmacy, Beni-Suef University, Beni-Suef, Egypt. Electronic address: feby.farag@yahoo.com.
authors.forename: Phoebe F
authors.initials: PF
authors.lastname: Lamie
authors.affiliation: BioChemistry Department, Cairo General Hospital, Egypt.
authors.forename: Waleed A M
authors.initials: WAM
authors.lastname: Ali
authors.affiliation: Laboratory of Growth Regulators, Centre of the Region Haná for Biotechnological and Agricultural Research, Institute of Experimental Botany ASCR & Palacký University, Šlechtitelů 27, 783 71, Olomouc, Czech Republic; Department of Physical Chemistry, Faculty of Science, Palacký University, 17. Listopadu 1192/12, 771 46, Olomouc, Czech Republic.
authors.forename: Vaclav
authors.initials: V
authors.lastname: Bazgier
authors.affiliation: 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, Czech Republic. Electronic address: lucie.rarova@upol.cz.
authors.forename: Lucie
authors.initials: L
authors.lastname: Rárová
mesh_terms: D000893:Anti-Inflammatory Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology; D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology; D001094:Arachidonate 5-Lipoxygenase / Q000737:chemistry / Q000378:metabolism*; D020134:Catalytic Domain; D045744:Cell Line, Tumor; D060326:Chemistry Techniques, Synthetic; D051545:Cyclooxygenase 1 / Q000378:metabolism; D051546:Cyclooxygenase 2 / Q000378:metabolism*; D052246:Cyclooxygenase 2 Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology; D015195:Drug Design; D006801:Humans; D007211:Indoles / Q000138:chemical synthesis* / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D016859:Lipoxygenase Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology; D062105:Molecular Docking Simulation; D012545:Schiff Bases / Q000737:chemistry
chemical_list: D000893:Anti-Inflammatory Agents; D000970:Antineoplastic Agents; D052246:Cyclooxygenase 2 Inhibitors; D007211:Indoles; D016859:Lipoxygenase Inhibitors; D012545:Schiff Bases; D001094:Arachidonate 5-Lipoxygenase; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2
keywords: Anti-inflammatory activity; Antiproliferative activity; Cyclooxygenase enzymes; Indole derivatives; Molecular docking study