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Synthesis and antinociceptive activities of some pyrazoline derivatives.

In the present study, some pyrazoline derivatives were synthesized to investigate their potential antinociceptive activities. 1-[(Benzoxazole/benzimidazole-2-yl)thioacetyl]pyrazoline derivatives were obtained by reacting 3,5-diaryl-1-(2-chloroacetyl)pyrazolines with 2-marcaptobenzoxazole/benzimidazole. The chemical structures of the compounds were elucidated by IR, (1)H NMR and FAB(+)-MS spectral data and Elemental Analyses. All of the compounds (100 mg/kg) exhibited significant antinociceptive activities in both hot plate and acetic acid-induced writhing tests. Naloxone (5 mg/kg) pre-treatment reversed the antinociceptive activities suggesting the involvement of opioid system in the analgesic actions. None of the compounds impaired motor coordination of animals when assessed in the Rota-Rod model. These results support the previous papers reporting the opioid sensitive antinociceptive activities of various benzoxazole/benzimidazole-pyrazoline derivative compounds.

Synthesis and Study of Antibacterial and Antifungal Activities of Novel 2-(((Benzoxazole/benzimidazole-2-yl)sulfanyl) acetylamino)thiazoles

Several 2-[[(benzoxazole/benzimidazole-2-yl)sulfanyl]acetylamino]thiazoles derivatives were synthesized by reacting 4-substituted-2-(chloroacetylamino)thiazoles with benzoxazole/benzimidazole-2-thioles in acetone and in the presence of K2CO3. The chemical structures of the compounds were elucidated by IR,1H-NMR, and FAB+-MS spectral data. Their antimicrobial activities againstMicrococcus luteus (NRLL B-4375),Bacillus cereus (NRRL B-3711),Proteus vulgaris (NRRL B-123),Salmonella typhimurium (NRRL B-4420),Staphylococcus aureus (NRRL B-767),Escherichia coli (NRRL B-3704),Candida albicans and Candida globrata (isolates obtained from Osmangazi Uni. Fac.of Medicine) were investigated and in this investigation, a significant level of activity was illustrated.

Synthesis and biological evaluation of some hydrazone derivatives as new anticandidal and anticancer agents

New hydrazone derivatives were synthesized via the nucleophilic addition-elimination reaction of 2-[(1-methyl-1H-tetrazol-5-yl)thio)]acetohydrazide with aromatic aldehydes/ketones. The compounds were tested in vitro against various Candida species and compared with ketoconazole. Genotoxicity of the most effective anticandidal compounds was evaluated by umuC and Ames assays. All compounds were also investigated for their cytotoxic effects on NIH3T3 and A549 cell lines. Compound 8 was the most effective antifungal derivative against C. albicans (ATCC-90028) with a MIC value of 0.05 mg/mL. Compound 5 can be identified as the most promising anticancer agent against A549 cancer cell lines due to its inhibitory effect on A549 cell lines and low toxicity to NIH3T3 cells.

New pyrazoline derivatives and their antidepressant activity

Some triazolo-pyrazoline derivatives were synthesized to investigate their potential antidepressant activities. The chemical structures of the compounds were elucidated by IR, NMR and FAB(+)-MS spectral data and elemental analyses. Antidepressant-like activities of the test compounds (100 mg/kg) were screened using both modified forced swimming and tail suspension tests. Rota-Rod test was performed for the examination of probable neurological deficits due to the test compounds, which may interfere with the test results. The test compounds in the series exhibited different levels of antidepressant activities when compared to reference drug fluoxetine. None of the test compounds changed motor coordination of animals when assessed in the Rota-Rod test. Therefore, experimental results in this study were not interfered with motor abnormalities.

Synthesis and the selective antifungal activity of 5,6,7,8-tetrahydroimidazo[1,2-a]pyridine derivatives.

Even though there are new classes of compounds now frequently used in treatment of fungal infections, the density of deeply invasive candidiasis has increased at least 10-fold during the past decade. Furthermore, many infections due to Candida species are actually refractory to antifungal therapy. In this present study, it was aimed to synthesize, new hydrazide derivatives of tetrahydroimidazo[1,2-a]pyridine and evaluate their anticandidal activity and cytotoxicity in vitro. The reaction of tetrahydroimidazo[1,2-a]pyridine-2-carboxylic acid hydrazides with various benzaldehydes gave tetrahydroimidazo[1,2-a]pyridine-2-carboxylic acid benzylidene hydrazide derivatives. The chemical structures of the compounds were elucidated and confirmed by IR, 1H NMR, MS-FAB+ spectroscopy and elemental analyses. Eight new tetrahydroimidazo[1,2-a]pyridine derivatives were synthesized and screened for their antifungal effects against a panel of ten human pathogenic Candida albicans, Candida glabrata, Candida krusei, Candida parapsilosis, Candida tropicalis, Candida utilis, and Candida zeylanoides using agar diffusion and broth microdilution assays, respectively. Furthermore, their cytotoxicity was tested against six mammalian cell lines. Among the analogues, the compound 5,6,7,8-tetrahydroimidazo[1,2-a]pyridine-2-carboxylic acid-(4-cyanobenzylidene) showed very strong inhibitory activity (up to MIC 0.016 mg/mL) against the screened Candida species. The same compound showed no in vitro toxicity up to 25 microg/mL concentration suggesting that its antifungal activity (MICs 0.016-1 mg/mL) is selective.

Synthesis and Biological Evaluation of Some Hydrazone Derivatives as Anti-inflammatory Agents

In the present study, some hydrazone derivatives were synthesized via the reaction of 3-cyclohexylpropionic acid hydrazide with various benzaldehydes. The chemical structures of the compounds were elucidated by spectroscopic techniques such as IR, 1 H-NMR and FAB-MS and elemental analyses. The compounds were evaluated for their anti- inflammatory and cytotoxic activities. Anti-inflammatory activity was determined in terms of inhibition of NF-! B, ROS generation and iNOS activity. Several derivatives inhibited NF-! B and iNOS, but no effect was observed on intracellular ROS generation. Furthermore no cytoxicity was observed. Biological activity compared with the chemical structural information suggests that different functional groups on the phenyl ring influence the physicochemical properties and thus modulate biological activity.

Synthesis and Antimicrobial Activities of Some 1-[(N, N-Disubstitutedthiocarbamoylthio)acetyl]-3,5-diaryl-2-pyrazolines

The increasing clinical importance of drug-resistant fungal and bacterial pathogens has lent additional urgency to microbiological research and new antimicrobial compound development. For this purpose, new pyrazoline derivatives were synthesized and evaluated for antimicrobial activity. Some 1-[(N, N-disubstitutedthiocarbamoylthio)acetyl]-3,5-diaryl-2-pyrazolines derivatives were synthesized by reacting 1-(chloroacetyl)-3,5-diaryl-2-pyrazolines with appropriate potassium salts of secondary amine dithiocarbamic acids. The chemical structures of the compounds were elucidated by IR, 1 H-NMR, and FAB+-MS spectral data. Their antimicrobial activities against Staphylococcus aureus (B-767), Escherichia coli (B-3704), Pseudomonas aeruginosa (ATCC 27853), Proteus vulgaris (NRLL B-123), and Candida albicans (NRRL-27077) were investigated. The results showed that some of the compounds have notable activity against S. aureus and C. albicans.

Effects of some 1,3,5-trisubstitued-2-pyrazoline derivatives on depression and anxiety parameters of mice

The aim of the present study was examining the effects of some 1,3,5-trisubstituted-2-pyrazoline derivatives on depression, anxiety and spontaneous locomotor activity parameters of mice. None of the compounds was effective at 50 mg/kg dose whereas at 100 and 200 mg/kg, pyrazoline-benzoxazole derivative test compound 4a and pyrazoline-benzimidazole derivative test compound 4d in the series were exhibited significant antidepressant effects in modified forced swimming tests. These two pyrazolines decreased the immobility and increased the swimming times of mice without any change in climbing durations suggesting the antidepressant-like effects of the test compounds. In spite of significant antidepressant effect, none of the compounds changed the exploratory parameters in hole-board tests or total numbers of spontaneous locomotor activities in activity cage measurements at any of the applied doses. In other words, neither anxiolytic nor sedative effects induced by the test compounds. The results obtained from this study supported the previous findings reporting the antidepressant activities of pyrazoline derivative compounds. Exact mechanism of the antidepressant action exhibited in the present study need to be clarified with further detailed investigations.

Synthesis of Thiadiazole Derivatives Bearing Hydrazone Moieties and Evaluation of Their Pharmacological Effects on Anxiety, Depression, and Nociception Parameters in Mice

Novel thiadiazole derivatives bearing hydrazone moieties were synthesized through the reaction of 2-[(5-methyl-1,3,4-thiadiazol-2-yl)thio)]acetohydrazide with aldehydes/ketones. The chemical structures of the compounds were elucidated by 1H-NMR, 13C-NMR, MS-FAB spectral data, and elemental analyses. Behavioral effects of the test compounds in mice were examined by hole-board, activity cage, tail suspension and modified forced swimming tests (MFST). Antinociceptive activities were evaluated using the hot-plate and tail-clip methods. Results of the experiments indicated that the test compounds did not significantly change the exploratory behaviors or locomotor activities of animals in the hole-board and activity cage tests, respectively. Administration of the reference drug fluoxetine (10 mg/kg) and compounds 3a, 3b, 3c, 3j, 3k, and 3l significantly shortened the immobility times of animals in the tail suspension and MFST tests, indicating the antidepressant-like effects of these derivatives. Morphine (10 mg/kg) and compounds 3a, 3b, 3c, 3d, 3e, 3j, 3k, and 3l increased the reaction times of mice in both the hot-plate and tail-clip tests, indicating the antinociceptive effects of these compounds. To the best of our knowledge, this is the first study of central nervous system activities of chemical compounds carrying thiadiazole and hydrazone moieties together on their structures.

Synthesis of some 4-arylidenamino-4H-1,2,4-triazole-3-thiols and their antituberculosis activity.

The increasing clinical importance of drug-resistant mycobacterial pathogens has lent additional urgency to microbiological research and new antimycobacterial compound development. For this purpose, new triazoles were synthesized and evaluated for antituberculosis activity. A series of 4-arylidenamino-4H-1,2,4-triazole-3-thiol derivatives (2a–n) were synthesized from the treatment of 4-amino-4H-1,2,4-triazoles-3-thiol (1) with the respective aldehydes and were evaluated for antituberculosis activity against Mycobacterium tuberculosis H37Rv (ATCC 27294), using the BACTEC 460 radiometric system and BACTEC 12B medium. Compound 2k showed an intereting activity at 6.25 μg/mL with a 87 percentage inhibition.