title: Synthesis of some novel heterocyclic compounds derived from diflunisal hydrazide as potential anti-infective and anti-inflammatory agents.
abstract: Three novel series of 2',4'-difluoro-4-hydroxybiphenyl-3-carboxylic acid derivatives namely 4-substituted-1,2,4-triazoline-3-thiones (4a-g); 2-substituted-1,3,4-thiadiazoles (5a-g) and 2-substituted-1,3,4-oxadiazoles (6a-g) have been synthesized. Twenty-one of the newly synthesized compounds were tested against various bacteria, fungi, yeast species and virus. In addition, we have replaced the carboxylic acid group of diflunisal with heterocycles and the anti-inflammatory activity of heterocycles reported here. Compound (5d) showed activity against Escherichia coli A1 and Streptococcus pyogenes ATCC-176 at a concentration of 31.25 microg/mL, whereas cefepime, the drug used as standard, has been found less active against the bacteria mentioned above. Compound (4b) has exhibited activity against Aspergillus variecolor and Trichophyton rubrum at a concentration of 31.25 and 15.25 microg/mL, whereas Amphotericin B, the drug used as standard, has been found less active against the yeast and fungi. The highest antiviral activity was found in the 1,3,4-thiadiazole derivative (5a) having a methyl group at 2nd position against Sindbis virus at 9.6 microg/mL. Compound (4c) exhibited the highest anti-inflammatory activity (73.03%) whereas diflunisal, the drug used as standard, has been found less active (24.16%). Compound (5f) presented similar antinociceptive activity with the standard drug (paw withdrawal latency was 19.21 s compared to that of diflunisal which was 19.14s, in hot plate test).
authors.affiliation: Marmara University, Faculty of Pharmacy, Department of Pharmaceutical Chemistry, Tibbiye Cad. No. 49, Haydarpasa, Istanbul 34668, Turkey. gkucukguzel@marmara.edu.tr
authors.forename: S Güniz
authors.initials: SG
authors.lastname: Küçükgüzel
authors.forename: Ilkay
authors.initials: I
authors.lastname: Küçükgüzel
authors.forename: Esra
authors.initials: E
authors.lastname: Tatar
authors.forename: Sevim
authors.initials: S
authors.lastname: Rollas
authors.forename: Fikrettin
authors.initials: F
authors.lastname: Sahin
authors.forename: Medine
authors.initials: M
authors.lastname: Güllüce
authors.forename: Erik
authors.initials: E
authors.lastname: De Clercq
authors.forename: Levent
authors.initials: L
authors.lastname: Kabasakal
mesh_terms: D000818:Animals; D000890:Anti-Infective Agents / Q000138:chemical synthesis* / Q000494:pharmacology; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000138:chemical synthesis* / Q000494:pharmacology; D001419:Bacteria / Q000187:drug effects; D004061:Diflunisal / Q000031:analogs & derivatives*; D005260:Female; D005658:Fungi / Q000187:drug effects; D006571:Heterocyclic Compounds / Q000138:chemical synthesis* / Q000494:pharmacology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008826:Microbial Sensitivity Tests; D015394:Molecular Structure; D010146:Pain / Q000188:drug therapy; D014780:Viruses / Q000187:drug effects
chemical_list: D000890:Anti-Infective Agents; D000894:Anti-Inflammatory Agents, Non-Steroidal; D006571:Heterocyclic Compounds; D004061:Diflunisal