title: Synthesis, antitumor activity and molecular docking study of novel benzofuran-2-yl pyrazole pyrimidine derivatives.
abstract: A new series of (benzofuran-2-yl)-1-phenyl-1H-pyrazol-4-yl) pyrimidine derivatives were synthesized from 3-(benzofuran-2-yl)-1-phenyl-1H-pyrazol-4-carbaldehyde (1) through different routes of cyclocondensation reactions. Condensation of 1 with active methylene compounds afforded compounds 2-8. The cyclization of 2 with chloroacetic acid, ortho substituted benzoic acid and/or ethanolamine gave compounds 9-12. Also condensation of 2 with hydrazine hydrate followed by cyclocondensation afforded corresponding triazines and pyrazole derivatives 18-27. Some docking studies of the newly prepared compounds as thymidylate synthase inhibitors have been done. Also the cytotoxic activity of some of the prepared compounds as a representative examples was evaluated against HEPG2 (human liver carcinoma cell line) in comparison with 5-fluorouracil (5-Fu).
authors.affiliation: Therapeutical Chemistry Department, National Research Center, Dokki, Cairo, Egypt. melzahar@hotmail.com
authors.forename: Magdy I
authors.initials: MI
authors.lastname: El-Zahar
authors.forename: Somaia S
authors.initials: SS
authors.lastname: Adb El-Karim
authors.forename: Mogedda E
authors.initials: ME
authors.lastname: Haiba
authors.forename: Mohammed A
authors.initials: MA
authors.lastname: Khedr
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000494:pharmacology*; D001572:Benzofurans / Q000138:chemical synthesis* / Q000494:pharmacology*; D002470:Cell Survival / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000138:chemical synthesis / Q000494:pharmacology; D056945:Hep G2 Cells; D006801:Humans; D008958:Models, Molecular; D015394:Molecular Structure; D011487:Protein Conformation; D011720:Pyrazoles / Q000138:chemical synthesis* / Q000494:pharmacology*; D011743:Pyrimidines / Q000138:chemical synthesis* / Q000494:pharmacology*; D013329:Structure-Activity Relationship; D013940:Thymidylate Synthase / Q000037:antagonists & inhibitors / Q000737:chemistry
chemical_list: D000970:Antineoplastic Agents; D001572:Benzofurans; D004791:Enzyme Inhibitors; D011720:Pyrazoles; D011743:Pyrimidines; D013940:Thymidylate Synthase