Selma Saraç

Synthesis and in vitro calcium antagonist activity of 4-aryl-7,7-dimethyl/1,7,7-trimethyl-1,2,3,4,5,6,7,8-octahydroquinazoline-2,5-dione derivatives

In this study, a series of 4-aryl-7,7-dimethyl and 1,7,7-trimethyl-1,2,3,4,5,6,7,8-octahydroquinazoline-2,5-diones (1-25) were synthesized by condensing urea or N-methylurea with 5,5-dimethyl-1,3-cyclohexanedione and appropriate aromatic aldehydes according to the Biginelli reaction. The structures of the compounds were confirmed by spectral data and elementary analysis. The calcium antagonist activity of the compounds was tested in vitro on isolated rat ileum and lamb carotid artery. Compounds 16 and 19 were the most active derivatives on isolated rat ileum compared with the standard nicardipine. On isolated aortic strips of lamb the calcium antagonist activity of compound 16 (maximum relaxant effect: 38.83+/-5.84%) was found as high as that of nicardipine (maximum relaxant effect: 35.50+/-4.16%) used as a reference drug.

Enantioseparation of 3,4-dihydroxyphenylalanine and 2-hydrazino-2-methyl-3-(3,4-dihydroxyphenyl)propanoic acid by capillary electrophoresis using cyclodextrins

The enantiomeric separations of 3,4-dihydroxyphenylalanine (dopa) and 2-hydrazino-2-methyl-3-(3,4-dihydroxyphenyl)propanoic acid (carbidopa) by capillary electrophoresis were studied using several native, neutral and anionic cyclodextrins as chiral additives and uncoated fused-silica capillaries. The effect of the type and concentration of the cyclodextrin added to 20 mM phosphate buffer (pH 2.5) on enantioseparation and migration times was studied. A high resolution value of 15.63 was obtained for dopa enantiomers with a buffer containing 20 mM single isomer, heptakis(2,3-diacetyl-6-sulfato)-beta-cyclodextrin. The enantiomers of carbidopa were separated using 20 mM carboxymethyl-beta-cyclodextrin as a chiral resolving agent. Both methods allowed the determination of 0.1% of the D-enantiomer (second migrating) in the presence of the L-enantiomer (first migrating) of dopa and carbidopa with a good precision. These methods also gave good results in terms of precision for both peak area, migration time, linearity and accuracy.

Synthesis, structural elucidation and pharmacological properties of some 5-acetyl-3,4-dihydro-6-methyl-4-(substituted phenyl)-2(1H) -pyrimidinones.

In this study, the synthesis of some new 5-acetyl-3,4-dihydro-6-methyl-4-(substituted phenyl)-2(1H)-pyrimidinones has been reported. The compounds were prepared by the Biginelli reaction of acetylacetone with aromatic aldehydes and urea. The structures of the compounds were characterized by UV, IR, 1H NMR, 13C NRM, mass spectra and elementary analysis. The calcium antagonistic activity of these compounds was tested in vitro on rat ileum precontracted with 4 x 10(-3) M barium chloride.

Studies on synthesis, chromatographic resolution, and antiinflammatory activities of some 2-thioxo-1,2,3,4-tetrahydropyrimidines and their condensed derivatives.

In this study, the synthesis of some new 2‐thioxo‐1,2,3,4‐tetrahydropyrimidines and their condensed derivatives, thiazolo[3,2‐α] pyrimidines, are described. The structures of the compounds were confirmed by IR, 1H‐NMR, 13C‐NMR, and mass spectroscopy. The direct high‐performance liquid chromatographic separation of the compounds on derivatized cellulose chiral stationary phases such as cellulose tris(3,5‐dimethylphenylcarbamate) (OD), cellulose tris(4‐methylphenylcarbamate) (OG), and cellulose tris(4‐methylbenzoate) (OJ) was studied. All of the compounds were screened for their antiinflammatory activity and also investigated histopathologically. Compounds 3 and 1a were found to be the most promising antiinflammatory agents in this group.

Analytical Resolution of 4-ARYL-1,2,3,4,5,6,7,8-Octahydroquinazoline-2-Thiones using a Cellulose Chiral Stationary Phase

Racemic 4-aryl-1,2,3,4,5,6,7,8-octahydroquinazoline-2-thiones were resolved into their enantiomers by HPLC on cellulose tris(4-methylbenzoate) coated on silica gel using ethanol:n-hexane (70:30) as a mobile phase. A convenient method for preparation of cellulose tris(4-methylbenzoate) chiral stationary phase was described and the enantiomers were characterized by some chromatographic data.

New Anti‐Seizure (Arylalkyl)azole Derivatives: Synthesis, In Vivo and In Silico Studies

(Arylalkyl)azoles are a class of antiepileptic compounds including nafimidone, denzimol, and loreclezole (LRZ). Nafimidone and denzimol are thought to inhibit voltage‐gated sodium channels (VGSCs) and enhance γ‐aminobutyric acid (GABA)‐mediated response. LRZ, a positive allosteric modulator of A‐type GABA receptors (GABAARs), was reported to be sensitive to Asn265 of the β2/β3 subunit. Here, we report new N‐[1‐(4‐chlorophenyl)‐2‐(1H‐imidazol‐1‐yl)ethylidene]hydroxylamine esters showing anticonvulsant activity in animal models, including the 6‐Hz psychomotor seizure test, a model for therapy‐resistant partial seizure. We performed molecular docking studies for our active compounds using GABAAR and VGSC homology models. They predicted high affinity to the benzodiazepine binding site of GABAAR in line with the experimental results. Also, the binding mode and interactions of LRZ in its putative allosteric binding site of GABAAR is elucidated.

Synthesis, anticonvulsant activity, and molecular modeling studies of novel 1-phenyl/1-(4-chlorophenyl)-2-(1H-triazol-1-yl)ethanol ester derivatives

A series of new ester derivatives were synthesized by the reaction of various acids with 1-phenyl/1-(4-chlorophenyl)-2-(1H-triazol-1-yl)ethanol and in vivo screened for their anticonvulsant activity. The title compounds were screened against MES and ScM seizure tests according to a modified version of the Epilepsy Therapy Screening Program (ETSP) protocol of the National Institutes of Health (NIH). Their neurotoxic effects were evaluated by the rotarod test. All the compounds showed protection against MES and/or ScM-induced seizures at 30 mg/kg without neurotoxicity. More compounds were found active in the ScM test and at lower dose than the MES test. Physicochemical and pharmacokinetic profiles of the compounds were predicted by QikProp. Using molecular docking approach we tried to get insights into their possible anticonvulsant mechanisms.