The complete mitochondrial genome of Talpa martinorum (Mammalia: Talpidae), a mole species endemic to Thrace: genome content and phylogenetic considerations.

The complete mitogenome sequence of Talpa martinorum, a recently described Balkan endemic mole, was assembled from next generation sequence data. The mitogenome is similar to that of the three other Talpa species sequenced to date, being 16,835 bp in length, and containing 13 protein-coding genes, two ribosomal RNA genes, 22 transfer RNA genes, an origin of L-strand replication, and a control region or D-loop. Compared to other Talpa mitogenomes sequenced to date, that of T. martinorum differs in the length of D-loop and stop codon usage. TAG and T-- are the stop codons for the ND1 and ATP8 genes, respectively, in T. martinorum, whilst TAA acts as a stop codon for both ND1 and ATP8 in the other three Talpa species sequenced. Phylogeny reconstructions based on Maximum Likelihood and Bayesian inference analyses yielded phylogenies with similar topologies, demonstrating that T. martinorum nests within the western lineage of the genus, being closely related to T. aquitania and T. occidentalis.

Wingless ligands and beta-catenin expression in the rat endometrium: The role of Wnt3 and Wnt7a/beta-catenin pathway at the embryo-uterine interface.

Wnt/beta-catenin signaling may play an essential role in endometrial decidualization, placentation, and the establishment of pregnancy. We investigate here the possible roles, immunolocalizations, and synthesis of the Wnt3, Wnt7a, and beta-catenin proteins in the rat endometrium during the estrous cycle and early postimplantation period. Wnt3 and Wnt7a had a similar localization and dynamic expression relative to the endometrial stages. Wnt7a immunostaining was not limited only to the luminal epithelial cells, but also to strong stainings in the stromal and endothelial cells. Wnt3, Wnt7a, and beta-catenin were highly synthesized and colocalized at the trophoblast-decidual interface; and were more obvious in the primary decidual zone, the GTCs, and the ectoplacental cone. Beta-catenin was strongly localized at the borders of the mature decidual cells; however, Wnt3 and Wnt7a immunolocalizations were decreased in those cells. As such, the immunolocalization of Wnt3, Wnt7a, and beta-catenin shifted with decidualization and placentation. The expression level of Wnt3, Wnt7a, and beta-catenin messenger RNAs increased in early pregnancy, and especially between Days 8.5 and 9.5. The dramatic changes in the expression of Wnt3, Wnt7a, and beta-catenin observed during the early days of pregnancy and the estrous cycle may indicate their roles in decidualization, stromal cell proliferation, and trophoblast invasion.

Synthesis and pharmacological activities of some new 2-[1-(6-methoxy-2-naphthyl)ethyl]-6-(substituted)benzylidene thiazolo[3,2-b]-1,2,4-triazole-5(6H)-one derivatives.

In this study, thirteen new compounds having a 2-[1-(6-methoxy-2-naphthyl)ethyl]-6-(substituted)benzylidenethiazolo[3,2-b]- 1,2,4-triazole-5(6H)-one structure were synthesised using N-[2-(6-methoxy-2-naphthyl)propanoyloxysuccinimide, N-[2-(6-methoxy-2-naphthyl)propanoyl]thiosemicarbazide and 3-[1-(6-methoxy-2-naphthyl)ethyl]-5-mercapto-1,2,4-triazole. The structures and physical properties of the compounds were elucidated by IR, 1H NMR, mass spectroscopy and elemental analysis. The antiinflammatory activity and gastric ulceration potential of the compounds were tested using naproxen as a reference compound.

Synthesis of some thiazolo[3,2-b]-1,2,4-triazole-5(6H)-ones and their novel Michael addition products with anti-inflammatory activities.

In this study, 21 new compounds having 2-methyl-6-benzylidenethiazolo[3,2-b]-1,2,4-triazol-5(6H)-one (2-4) and 2-methyl-6-(alpha-aminobenzyl)thiazolo[3,2-b]-1,2,4-triazole-5-ol (2a-4g) structures were synthesized. The structures of the compounds were proved by spectral and elemental analysis. All of the compounds synthesized were tested for their anti-inflammatory actively and ulcerogenic potential in mice at 10, 20 and 40 mg/kg dose levels. Compound 4b showed higher anti-inflammatory activity than the analogue derivatives and indometacin (CAS 53-86-1), used as a reference drug, at 10 mg/kg dose level. Generally, the compounds were found to be more reliable than indometacin since they did not cause any reaction in the stomach.

4-aryl-6,6-dimethyl-1,2,3,4,5,6,7,8-octahydroquinazoline-2,5-diones: synthesis, chromatographic resolution and pharmacological activity.

In this study, a series of 4-aryl-6,6-dimethyl-1,2,3,4,5,6,7,8- octahydroquinazoline-2,5-diones were synthesized by condensing urea with 4,4-dimethyl-1,3-cyclohexanedione and appropriate aromatic aldehydes according to the Biginelli reaction. The structures of the compounds were characterized by spectroscopic methods. The racemic compounds were resolved into the enantiomers by HPLC on amylose tris(3,5-dimethylphenylcarbamate) (Chiralpak AD). The compounds were tested in vitro for their calcium antagonistic activities. BaCl2-induced contractions of rat ileum were inhibited dose-dependently. Compounds 3 and 5 exerted weak calcium antagonistic activity on smooth muscles compared with the standard, nicardipine.

6-Benzylidenethiazolo[3,2-b]-1,2,4-triazole-5(6H)-ones substituted withibuprofen: synthesis, characterization and evaluation of anti-inflammatory activity.

In this study, the synthesis of 3-[1-(4-(2-methylpropyl)phenyl)ethyl]-1,2,4-triazole-5-thione (2) and its condensed derivatives 6-benzylidenethiazolo[3,2-b]-1,2, 4-triazole-5(6H)-ones (2a-u) are described. The structures of the compounds were elucidated by spectral and elemental analysis. In the pharmacological studies, anti-inflammatory activities of these compounds have been screened. Among the compounds examined, the compounds 2 and 2g possessed the most prominent and consistent activity. In gastric ulceration studies the synthesized compounds were generally found to be safe at a 200 mg/kg dose level.

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-a]pyrimidines, are described. The structures of the compounds were confirmed by 1R, 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.

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.

Synthesis and anti-inflammatory activities of some thiazolo[3,2-a]pyrimidine derivatives.

Sixteen new 2-benzylidene-7-methyl-3-oxo-5-(substituted phenyl)-2, 3-dihydro-5H-thiazolo[3,2-a]pyrimidine-6-carboxylic acid methyl esters (1a-4d) have been synthesized by reacting 1,2,3,4-tetrahydropyrimidine-2-thiones (1-4) with chloroacetic acid and appropriate benzaldehydes in a single step. Their structures have been proved by IR, 1H NMR, mass spectra and elemental analysis. The compounds were tested for their anti-inflammatory activities. Test results revealed that compounds 1b, 1c, 4a and 4c exerted moderate anti-inflammatory activity at the 100 mg/kg dose level compared with indomethacin.

Synthesis and evaluation of anti-inflammatory activity of some thiazolo[3,2-b]-1,2,4-triazole-5(6H)-ones and their Michael addition products.

Thiazolo[3,2-b]-1,2,4-triazole-5(6H)-ones (4-10) were obtained in a one step synthesis by heating 3-aryl-5-mercapto-1,2,4-triazoles (3a-d) with chloroacetic acid and appropriate aromatic aldehyde in acetic acid and acetic anhydride in the presence of anhydrous NaOAc. Michael type addition of cyclic secondary amines (N-methylpiperazine, piperidine) to 4-10 gave 2-phenyl-6-(alpha-aminoarylmethyl)thiazolo[3,2-b]-1,2,4-triazole-5 -ols (4a-10b). The structures of the compounds were confirmed by spectral and elementary analysis. The compounds synthesized in previous and present studies were investigated for their anti-inflammatory activities.

Condensed heterocyclic compounds: synthesis and antiinflammatory activity of novel thiazolo[3,2-alpha] pyrimidines.

In this study, thirty six new 2-benzylidene-7-methyl-3-oxo-5- phenyl-2,3-dihydro-5H-thiazolo[3,2-alpha]pyrimidine-6-carboxylic acid methyl esters were synthesized and characterized by spectral, crystallographic, and elemental analysis. The antiinflammatory activity of the compounds was tested by the carrageenan hind paw edema test. It was found that compound 6a having a 2-meth-oxyphenyl group at position 5 and a benzylidene group at position 2 was the most potent compound in this series. All the compounds that were tested for ulcer activity gave positive results.

Synthesis, chemical and pharmacological properties of some 4-aryl-1,2,3,4,5,6,7,8-octahydroquinazoline-2,5-diones.

A series of 4-aryl-1,2,3,4,5,6,7,8-octahydroquinazoline-2,5-diones were synthesized by condensing urea with 1,3-cyclohexanedione and appropriate aromatic aldehydes according to the Biginelli reaction. The structures of the compounds were confirmed by elementary and spectroscopic analysis. The compounds synthesized were tested in vitro for their calcium antagonistic activities. BaCl2-induced contractions of rat ileum were inhibited dose-dependently. Compounds 3-8 exerted weak calcium antagonistic activity on smooth muscles compared with the standard nicardipine.

4-aryl-5-oxo-1,2,3,4,5,6,7,8-octahydroquinazoline-2-thione derivatives: synthesis, enantiomeric separation and in vitro screening as calcium antagonists.

Fourteen new 4-aryl-5-oxo-1,2,3,4,5,6,7,8-octahydroquinazoline-2-thione derivatives were synthesized and screened in vitro for their calcium antagonistic activities. The compounds were prepared by reacting 1,3-cyclo-hexanedione with appropriate aromatic aldehydes and thiourea under modified Biginelli reaction conditions. The structures of the compounds were proved by IR, 1H-NMR, mass spectroscopy and elemental analysis. The compounds synthesized exerted calcium antagonistic action on smooth musculature by inhibiting BaCl2-induced contractions of isolated rat ileum. It was found that compound 12l having 3-methoxyphenyl group at the 4th position was the most potent compound in this series (pEC50: 4.00 +/- 0.20). Rasemic compound 12l was resolved into its enantiomers by high performance liquid chromatography (HPLC) using a commercially available cellulose tris(p-methylbenzoate) chiral stationary phase, known as Chiralcel OJ. The enantiomeric ratio was validated and peak identification for each enantiomer was established according to their optical rotation sign.

New thiazolo[3,2-a] pyrimidine derivatives, synthesis and calcium antagonistic activities.

The synthesis of a series of thiazolo[3,2-a]pyrimidine derivatives were described. The structures of the compounds were elucidated by IR, 1H-NMR, 13C and elementary analysis. The compounds were evaluated for their calcium antagonistic activities using nifedipine as standard compound. All of the compounds were found to be less potent than nifedipine.

3,4-diaminopyridine in childhood myasthenia: double-blind, placebo-controlled trial.

Eleven patients with congenital and five with juvenile myasthenia gravis, aged 5 to 24 years, were given 3,4-diaminopyridine in a double-blind, placebo-controlled, crossover study. Clinical improvement was observed in 5 of 11 congenital myasthenia patients, and placebo effect, in 3 of 11. Juvenile myasthenia patients did not respond. Single-fiber electromyographic studies did not reveal any changes correlating with the clinical status of the patient. This study demonstrates the importance of double-blind and placebo-controlled studies to determine the effect of 3,4-diaminopyridine in congenital myasthenia. This drug may have different effects on various presynaptic and postsynaptic defects of neuromuscular transmission resulting in congenital myasthenia syndromes.

Synthesis of some 2-arylpropionic acid amides as prodrugs.

The synthesis of amide prodrugs of some 2-arylpropionic acids (ibuprofen, naproxen, diclofenac and ketorolac) and the enantiomeric separation of these compounds are reported in this paper. The compounds were prepared from the corresponding 2-arylpropionic acids and (R-(-)-2-amino-1-butanol in the presence of N,N'-dicyclohexylcarbodiimide (DCC). Enantiomers were separated by preparative chromatography or crystallisation. The structure were confirmed by infrared, nuclear magnetic resonance and elementary analysis. The compounds prepared in the study have significant analgesic activity.

New naphthyloxyalkyl beta-diketone and 3,5-dimethylisoxazole derivatives as potential antiviral agents.

Ten new compounds having 3-[(2-naphthyloxy)alkyl]-2,4-pentanedione and 4-[(2-naphthyloxy)alkyl]-3,5-dimethylisoxazole structures were synthesized and their cytotoxicities and antiviral activities investigated. 3-[6-(2-Naphthyloxy)hexyl]-2,4-pentandione possessing inhibitory activity on the replication of both adenovirus type 5 and poliovirus type 1 at 20 micrograms/ml was the most active compound in the series.

Synthesis and biological activities of some 3,6-disubstituted thiazolo[3,2-b][1,2,4]triazoles.

Some new 2,3-dihydro-3-hydroxy-6-phenyl-3-(4-substituted- (phenylthiazolo[3,2-b][1,2,4]triazole derivatives were synthesized as antifungal agents. After their structures were confirmed by microanalysis and IR and NMR spectral analysis, their antifungal activities against Candida albicans, Candida parapsilosis, Candida stellatoidea, and Candida pseudotropicalis were investigated. Contrary to our expectations, all proved to have poor antifungal activities. Because 2,4-dihydro-3H-1,2,4-triazol-3-ones are a new class of anticonvulsant agents, a series of thiazolo[3,2-b][1,2,4]triazoles was evaluated for anticonvulsant activity and observed as potential anticonvulsant candidates. All compounds examined exhibited activity against both maximal electroshock and pentylene tetrazole-induced seizures in mice.