Synthesis, anticonvulsant and antimicrobial activities of some new 2-acetylnaphthalene derivatives.
In this study, as a continuation of our research for new (arylalkyl)imidazole anticonvulsant compounds, the design, synthesis and anticonvulsant/antimicrobial activity evaluation of a series of 2-acetylnaphthalene derivatives have been described. Molecular design of the compounds has been based on the modification of nafimidone [1-(2-naphthyl)-2-(imidazol-1-yl)ethanone], which is a representative of the (arylalkyl)imidazole anticonvulsant compounds as well as its active metabolite, nafimidone alcohol (3, 4). In general, these compounds were variously substituted at the alkyl chain between naphthalene and imidazole rings and subjected to some other modifications to evaluate additional structure-activity relationships. The anticonvulsant activity profile of those compounds was determined by maximal electroshock seizure (MES) and subcutaneous metrazol (scM) seizure tests, whereas their neurotoxicity was examined using rotarod test. All the ester derivatives of nafimidone alcohol (5a-h), which were designed as prodrugs, showed anticonvulsant activity against MES-induced seizure model. Four of the most active compounds were chosen for further anticonvulsant evaluations. Quantification of anticonvulsant protection was calculated via the ip route (ED(50) and TD(50)) for the most active candidate (5d). Observed protection in the MES model was 38.46mgkg(-1) and 123.83mgkg(-1) in mice and 20.44mgkg(-1), 56.36mgkg(-1) in rats, respectively. Most of the compounds with imidazole ring also showed antibacterial and/or antifungal activities to a certain extent in addition to their anticonvulsant activity.
Karakurt
Arzu
A
Pharmaceutical Chemistry Department, Faculty of Pharmacy, Hacettepe University, 06100 Sihhiye Ankara, Turkey. akarakurt@inonu.edu.tr
Ozalp
Meral
M
Işik
Samil
S
Stables
James P
JP
Dalkara
Sevim
S
D000818:Animals; D000890:Anti-Infective Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000627:therapeutic use; D000927:Anticonvulsants / Q000138:chemical synthesis* / Q000737:chemistry / Q000627:therapeutic use; D018360:Crystallography, X-Ray; D007093:Imidazoles / Q000737:chemistry; D008968:Molecular Conformation; D009278:Naphazoline / Q000031:analogs & derivatives / Q000737:chemistry; D009281:Naphthalenes / Q000138:chemical synthesis / Q000737:chemistry* / Q000627:therapeutic use; D051381:Rats; D012640:Seizures / Q000139:chemically induced / Q000188:drug therapy; D013329:Structure-Activity Relationship
D000890:Anti-Infective Agents; D000927:Anticonvulsants; D007093:Imidazoles; D009281:Naphthalenes; C503376:2-acetylnaphthalene; C052468:nafimidone alcohol; C029899:imidazole; D009278:Naphazoline