title: Design, synthesis and molecular docking study of novel quinoxalin-2(1H)-ones as anti-tumor active agents with inhibition of tyrosine kinase receptor and studying their cyclooxygenase-2 activity.
abstract: On continuation to our work, new quinoxalin-2(1H)-ones were synthesized to study their cytotoxic effect against HepG-2 and MCF-7 with their effect on the human tyrosine kinase (TRK). Compounds 12, 18, 15, 13, 11a, 20 and 16, respectively, were found to be more potent than cisplatin against HepG2 and selective to TRK. Also, compounds 12, 18, 20, 13, 14, and 22, respectively, exhibited decidedly activity against MCF-7 and selectivity against human TRK compared to cisplatin. A molecular docking study was also performed to gain comprehensive understanding into plausible binding modes and to conclude the structure activity relationships of the synthesized compounds. Moreover, anti-inflammatory activity was studied. Compounds 12, 15, 18 and 22 were found to be potent and selective against COX-2.
authors.affiliation: Department of Chemistry of Natural and Microbial Products, Division of Pharmaceutical and Drug Industries, National Research Centre, Dokki, 12622, Cairo, Egypt. Electronic address: sh12galal@hotmail.com.
authors.forename: Shadia A
authors.initials: SA
authors.lastname: Galal
authors.affiliation: Department of Chemistry of Natural and Microbial Products, Division of Pharmaceutical and Drug Industries, National Research Centre, Dokki, 12622, Cairo, Egypt.
authors.forename: Sarah H M
authors.initials: SH
authors.lastname: Khairat
authors.affiliation: Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Cairo University, Cairo, Egypt.
authors.forename: Fatma A F
authors.initials: FA
authors.lastname: Ragab
authors.affiliation: Department of Chemistry of Natural and Microbial Products, Division of Pharmaceutical and Drug Industries, National Research Centre, Dokki, 12622, Cairo, Egypt.
authors.forename: Ahmed S
authors.initials: AS
authors.lastname: Abdelsamie
authors.affiliation: Department of Biochemistry, Division of Genetic Engineering and Biotechnology, National Research Centre, Dokki, 12622, Cairo, Egypt.
authors.forename: Mamdouh M
authors.initials: MM
authors.lastname: Ali
authors.affiliation: Department of Pharmaceutical Chemistry, Institute of Pharmacy, Freie University Berlin, Koenigin Luise Strasse, Berlin 14195, Germany.
authors.forename: Salwa M
authors.initials: SM
authors.lastname: Soliman
authors.affiliation: Department of Pharmaceutical Chemistry, Institute of Pharmacy, Freie University Berlin, Koenigin Luise Strasse, Berlin 14195, Germany.
authors.forename: Jérémie
authors.initials: J
authors.lastname: Mortier
authors.affiliation: Department of Pharmaceutical Chemistry, Institute of Pharmacy, Freie University Berlin, Koenigin Luise Strasse, Berlin 14195, Germany.
authors.forename: Gerhard
authors.initials: G
authors.lastname: Wolber
authors.affiliation: Department of Chemistry of Natural and Microbial Products, Division of Pharmaceutical and Drug Industries, National Research Centre, Dokki, 12622, Cairo, Egypt.
authors.forename: Hoda I
authors.initials: HI
authors.lastname: El Diwani
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D049109:Cell Proliferation / Q000187:drug effects; D051546:Cyclooxygenase 2 / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D015195:Drug Design; D004354:Drug Screening Assays, Antitumor; D004791:Enzyme Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D056945:Hep G2 Cells; D006801:Humans; D061986:MCF-7 Cells; D062105:Molecular Docking Simulation; D015394:Molecular Structure; D011810:Quinoxalines / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D020794:Receptor Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D013329:Structure-Activity Relationship
chemical_list: D000970:Antineoplastic Agents; D004791:Enzyme Inhibitors; D011810:Quinoxalines; D051546:Cyclooxygenase 2; D020794:Receptor Protein-Tyrosine Kinases
keywords: Antitumor activity; Cyclooxygenase-2; Docking; Protein tyrosine kinase; Quinoxalines; Synthesis