title: Synthesis, characterization, and biological-pharmacological evaluation of new phosphazenes bearing dioxybiphenyl and schiff base groups.
abstract: A new spirocyclophosphazene, 2,2-bis(2-formylphenoxy)-4,4,6,6-bis[spiro(2',2″-dioxy-1'-1″-biphenylyl)]cyclotriphosphazene (3), was obtained from the reaction of 2,2-dichloro-4,4,6,6-bis[spiro(2',2″-dioxy-1'-1″-biphenylyl)]cyclotriphosphazene (2) with 2-hydroxybenzaldehyde. New phosphazene derivatives bearing Schiff base and dioxybiphenyl groups have been synthesized by the reactions of 3 with different amines. The structures of the compounds were defined by elemental analysis, IR, (1) H, (13) C, and (31) P NMR spectroscopy. All the synthesized compounds were screened for their antibacterial activity against both types of Gram-negative and Gram-positive bacteria. The most potent antibacterial compound of this series was compound 12 which has the low MIC value of 3.75-0.9375 µg/mL. Both minimal inhibitory concentrations (MIC) and inhibition zones were determined in order to monitor the efficacy of the synthesized compounds. New compounds were also screened for anticonvulsant, CNS depressant, and sedative-hypnotic activity. After i.p. injection to mice at doses of 30, 100, and 300 mg/kg body weight phosphazenes were examined in the maximal electroshock-induced seizure (MES) and subcutaneous pentylenetetrazole (scPTZ) induced seizure models in mice. The neurotoxicity was assessed using the rotorod method. Compounds 4, 5, and 11 were found to be active in both MES screen and scPTZ screen at 0.5 h. All except 12 showed more than 44% decrease in locomotor activity after 1 h of compound administration via actophotometer screen. CNS-depressant activity screened with the help of the forced swim method resulted in some potent compounds. Except for 7 and 12 other tested compounds were found to exhibit potent CNS depressants activity as indicated by increased immobility time.
authors.affiliation: Education Faculty, Science Education Department, Firat University, Elazig, Turkey. cilerol@yahoo.com
authors.forename: Erol
authors.initials: E
authors.lastname: Cil
authors.forename: Mehmet Ali
authors.initials: MA
authors.lastname: Tanyildizi
authors.forename: Furkan
authors.initials: F
authors.lastname: Ozen
authors.forename: Mustafa
authors.initials: M
authors.lastname: Boybay
authors.forename: Mustafa
authors.initials: M
authors.lastname: Arslan
authors.forename: Ahmet Orhan
authors.initials: AO
authors.lastname: Gorgulu
mesh_terms: D000818:Animals; D000900:Anti-Bacterial Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology / Q000633:toxicity; D000927:Anticonvulsants / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology / Q000633:toxicity; D001522:Behavior, Animal / Q000187:drug effects; D001713:Biphenyl Compounds / Q000737:chemistry*; D004305:Dose-Response Relationship, Drug; D006090:Gram-Negative Bacteria / Q000187:drug effects / Q000254:growth & development; D006094:Gram-Positive Bacteria / Q000187:drug effects / Q000254:growth & development; D006993:Hypnotics and Sedatives / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology / Q000633:toxicity; D007928:Lethal Dose 50; D051379:Mice; D008826:Microbial Sensitivity Tests; D015394:Molecular Structure; D009943:Organophosphorus Compounds / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology* / Q000633:toxicity; D012545:Schiff Bases / Q000737:chemistry*; D012640:Seizures / Q000188:drug therapy; D013141:Spiro Compounds / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology* / Q000633:toxicity; D013329:Structure-Activity Relationship
chemical_list: D000900:Anti-Bacterial Agents; D000927:Anticonvulsants; D001713:Biphenyl Compounds; D006993:Hypnotics and Sedatives; D009943:Organophosphorus Compounds; D012545:Schiff Bases; D013141:Spiro Compounds