Synthesis of some 1-(2-naphthyl)-2-(imidazole-1-yl)ethanone oxime and oxime ether derivatives and their anticonvulsant and antimicrobial activities.
In this study, oxime and oxime ether derivatives of anticonvulsant nafimidone [1-(2-naphthyl)-2-(imidozole-1-yl)ethanone] were prepared as potential anticonvulsant compounds. Nafimidone oxime was synthesized by the reaction of nafimidone and hydroxylamine hydrochloride. O-Alkylation of the oxime by various alkyl halides gave the oxime ether derivatives. Anticonvulsant activity of the compounds was determined by maximal electroshock (MES) and subcutaneous metrazole (scMet) tests in mice and rats according to procedures of the Antiepileptic Drug Development (ADD) program of the National Institutes of Health (NIH). In addition to anticonvulsant evaluation, compounds were also screened for possible antibacterial and antifungal activities because of the structural resemblance to the azole antifungals, especially to oxiconazole. All compounds were evaluated against three human pathogenic fungi and four bacteria using the microdilution method. Most of the compounds exhibited both anticonvulsant and antimicrobial activities; the O-alkyl substituted compounds (2, 3, 4 and 5) were found to be more active than the O-arylalkyl substituted compounds in both screening paradigms.
Karakurt
A
A
Pharmaceutical Chemistry Department, Faculty of Pharmacy, Hacettepe University, 06100 Sihhiye-Ankara, Turkey.
Dalkara
S
S
Ozalp
M
M
Ozbey
S
S
Kendi
E
E
Stables
J P
JP
D000818:Animals; D000900:Anti-Bacterial Agents; D000890:Anti-Infective Agents / Q000009:adverse effects / Q000138:chemical synthesis* / Q000494:pharmacology*; D000927:Anticonvulsants / Q000009:adverse effects / Q000138:chemical synthesis* / Q000494:pharmacology* / Q000627:therapeutic use; D001419:Bacteria / Q000187:drug effects; D018360:Crystallography, X-Ray; D015195:Drug Design; D004353:Drug Evaluation, Preclinical; D004597:Electroshock; D004987:Ethers / Q000009:adverse effects / Q000138:chemical synthesis* / Q000494:pharmacology / Q000627:therapeutic use; D005658:Fungi / Q000187:drug effects; D006801:Humans; D007536:Isomerism; D051379:Mice; D008826:Microbial Sensitivity Tests; D008968:Molecular Conformation; D009278:Naphazoline / Q000009:adverse effects / Q000031:analogs & derivatives / Q000138:chemical synthesis* / Q000494:pharmacology / Q000627:therapeutic use; D010091:Oximes / Q000009:adverse effects / Q000138:chemical synthesis* / Q000494:pharmacology / Q000627:therapeutic use; D010433:Pentylenetetrazole / Q000494:pharmacology; D051381:Rats; D012018:Reflex / Q000187:drug effects; D012640:Seizures / Q000188:drug therapy; D013329:Structure-Activity Relationship
D000900:Anti-Bacterial Agents; D000890:Anti-Infective Agents; D000927:Anticonvulsants; D004987:Ethers; D010091:Oximes; D009278:Naphazoline; C038671:nafimidone; D010433:Pentylenetetrazole