title: DNA binding, antiviral activities and cytotoxicity of new furochromone and benzofuran derivatives.
abstract: Bromination of visnagin (1) afforded 9-bromovisnagin (2) which on its alkaline hydrolysis afforded the 3-acetyl benzofuran derivative (3). The condensation of (3) with hydrazine hydrate, phenylhydrazine and/or hydroxylamine hydrochloride afforded the corresponding pyrazole derivatives (4a, b) and isoxazole derivative (4c). On the other hand, when compound 3 was condensed with some aromatic aldehydes, this yielded corresponding α, β-unsaturated keto derivatives (5a-e). Furthermore, when 1 was subjected to chlorosulfonation, the visnaginsulfonylchloride derivative 6 was afforded, which on amidation using morpholine, a sulonamido derivative (7) was obtained. Alkaline hydrolysis of the latter compound yielded 7-N-morpholinosulsamidobenzofuran (8) which was condensed with some aromatic aldehydes to yield the corresponding chalcone compounds (9a-e). Demethylation of visnagin afforded norvisnagin (10). The reaction of 10 with ethylbromoacetate in dry acetone yielded the ester benzopyran derivative (11) which reacted with hydrazine hydrate to afford the corresponding hydrazide derivative (12) and this was condensed with 3,4,5-trimethoxybenzaldehyde to give the corresponding hydrazone (13). A thaizolidinone derivative (14) was obtained by condensation of (13) with thioglycolic acid. Chloromethylation of norvisnagin afforded a 4-chloromethyl derivative (15) which reacted with different primary and secondary amines to yield the corresponding ethylamino derivative (16a, b). Moreover, mannich bases (16a, b) and (17a-c) were obtained by reacting norvisnagin with different primary and secondary amines in the presence of formalin but benzoylation of (16a, b) and (17a-c) afforded 4-oxybenzoyl derivative (18a-e). The prepared compounds were tested for their interaction with DNA; bromovisnagin 2 showed the highest affinity and compounds 6, 15, 8a, > 14, > 16b, 17a, and 16a showed moderate activity in decreasing potency. Moreover, compound 2 also was the most active as antiviral agent toward HS-I virus and compounds 6, 7, 15, 14, 16a, and 18a were found to be moderately active. CD(50) of the active compounds were also measured.
authors.affiliation: Chemistry of Natural Products, National Research Center, Dokki, Cairo 72427, Egypt. ommryan@yahoo.com
authors.forename: Omaima Mohamed
authors.initials: OM
authors.lastname: Abdelhafez
authors.forename: Nehad Ahmed
authors.initials: NA
authors.lastname: Abedelatif
authors.forename: Farid A
authors.initials: FA
authors.lastname: Badria
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000737:chemistry* / Q000494:pharmacology*; D000998:Antiviral Agents / Q000138:chemical synthesis* / Q000494:pharmacology*; D001572:Benzofurans / Q000138:chemical synthesis* / Q000494:pharmacology*; D001667:Binding, Competitive / Q000187:drug effects; D047188:Chalcones / Q000138:chemical synthesis / Q000494:pharmacology; D002522:Chlorocebus aethiops; D002867:Chromones / Q000138:chemical synthesis* / Q000494:pharmacology*; D003124:Colorimetry; D003460:Crystallization; D004247:DNA / Q000378:metabolism*; D055808:Drug Discovery; D018259:Herpesvirus 1, Human / Q000187:drug effects; D006801:Humans; D007202:Indicators and Reagents; D007666:Khellin / Q000138:chemical synthesis / Q000494:pharmacology; D009682:Magnetic Resonance Spectroscopy; D008352:Mannich Bases; D013058:Mass Spectrometry; D013055:Spectrophotometry, Infrared; D017550:Spectroscopy, Fourier Transform Infrared; D014709:Vero Cells
chemical_list: D000970:Antineoplastic Agents; D000998:Antiviral Agents; D001572:Benzofurans; D047188:Chalcones; D002867:Chromones; D007202:Indicators and Reagents; D008352:Mannich Bases; D007666:Khellin; D004247:DNA; C044999:visnagin