title: Antitumor and antimicrobial activities of some hetero aromatic benzofurans derived from naturally occurring visnagin.
abstract: Bromination of visnaginone (1) yielded the dibromo derivative (2), which upon methylation with methyl iodide gave 1-(2,7-dibromo-4,6-dimethoxybenzofuran-5-yl) ethanone (3). Compound (3) reacted with dimethylformamide dimethylacetal to give (4). The reaction of (3) with aromatic aldehydes namely (vanillin, benzaldehyde and 3-anisaldehyde) in ammonium acetate, malononitrile and/or butyric cyanoanhydride gave the 2-amino substituted nicotinonitriles (5a-c) and the 2-hydroxyl substituted nicotinonitriles (7a-c), respectively, while in piperidine gave (E)-1-(2,7-dibromo-4,6-dimethoxybenzofuran-5-yl)-3-(substituted)prop-2-en-l-one (11a-c). (5a) was hydrolyzed with sulfuric acid on cold to give the nicotinic acid derivative (6a). When compound (3) reacted with hydrazines and aromatic amines, it gave the Schiff bases (8a,b) and (10a,b), respectively. (8b) reacted with thioglycolic acid to give the thiazolidin-4-one (9b). When (11a-c) reacted with thiourea, it gave the pyrimidine derivatives (12a-c). (11a,b) also reacted with butyric cyanoanhydride and hydroxylamine hydrochloride to give (13a,b) and (15a,b), respectively. When the carboxylate (13a) was treated with 2,4-dinitroaniline, it gave the carboxamide (14a). Compounds (11b,c) reacted with hydrazine derivatives (hydrazine hydrate and phenylhydrazine) yielding the substituted pyrazole derivatives (16b,c) and (17b,c), respectively. All the structures of the synthesized compounds were elucidated by elemental analyses and spectral data. The newly synthesized benzofuran compounds showed a strong to moderate cytotoxicity against liver HEPG2 cancer cell line compared to 5-fluorouracil and doxorubicin (the anticancer agents). Compounds (2, 6a, 13a, 14a, 16c and 17b) were the most active compounds in descending order. The synthesized compounds were also tested for their antimicrobial activity. Compound (10b) showed the highest activity against all the tested strains followed by 6, 10a, 5a, 8b and 7a in descending order.
authors.affiliation: Natural Products Department, National Research Center, Dokki, Cairo, Egypt.
authors.forename: Sally S
authors.initials: SS
authors.lastname: El-Nakkady
authors.forename: Hanaa F
authors.initials: HF
authors.lastname: Roaiah
authors.forename: Weam S
authors.initials: WS
authors.lastname: El-Serwy
authors.forename: Abdel Mohsen
authors.initials: AM
authors.lastname: Soliman
authors.forename: Sherein I Abd
authors.initials: SI
authors.lastname: El-Moez
authors.forename: Adel A H
authors.initials: AA
authors.lastname: Abdel-Rahman
mesh_terms: D000890:Anti-Infective Agents / Q000138:chemical synthesis / Q000494:pharmacology*; D000903:Antibiotics, Antineoplastic / Q000494:pharmacology; D000964:Antimetabolites, Antineoplastic / Q000494:pharmacology; D000972:Antineoplastic Agents, Phytogenic / Q000138:chemical synthesis / Q000494:pharmacology*; D001419:Bacteria / Q000187:drug effects / Q000254:growth & development; D001572:Benzofurans / Q000138:chemical synthesis / Q000494:pharmacology*; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D052978:Disk Diffusion Antimicrobial Tests; D004305:Dose-Response Relationship, Drug; D004317:Doxorubicin / Q000494:pharmacology; D005472:Fluorouracil / Q000494:pharmacology; D005658:Fungi / Q000187:drug effects / Q000254:growth & development; D056945:Hep G2 Cells; D006801:Humans; D020128:Inhibitory Concentration 50; D007666:Khellin / Q000031:analogs & derivatives* / Q000737:chemistry / Q000494:pharmacology; D015394:Molecular Structure; D013329:Structure-Activity Relationship
chemical_list: D000890:Anti-Infective Agents; D000903:Antibiotics, Antineoplastic; D000964:Antimetabolites, Antineoplastic; D000972:Antineoplastic Agents, Phytogenic; D001572:Benzofurans; D007666:Khellin; D004317:Doxorubicin; C044999:visnagin; D005472:Fluorouracil