Essential oil chemical composition, antimicrobial, anticancer, and antioxidant effects of Thymus convolutus Klokov in Turkey.

In this study, the chemical composition, antimicrobial, antioxidant, and anticancer effects of Thymus convolutus Klokov oil and its main compound camphor were investigated. The oil was isolated from T. convolutus using hydrodistillation method, analyzed by gas chromatography/mass spectrometry (GC-MS), and 66 compounds were identified. The main component was determined as camphor at 16.6%. The antioxidant properties were identified with the DPPH (2,2'-diphenyl-1-picrylhydrazyl) radical-scavenging method and, 33.39 ± 0.25% DPPH was scavenging in 1000 µg/mL of essential oil. The strong antimicrobial activity was observed against Escherichia coli, Enterobacter aerogenes, Proteus vulgaris, and Pseudomonas aeruginosa with MIC values of 125 µg/mL. Aspergillus flavus was more sensitive (28%) against T. convolutus essential oil than other fungi. The cytotoxic effect of oil was analyzed by MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide) method. Camphor was effective on human hepatoma cells (Hep3B) at concentrations of 1 mg/mL, 500, 250, and 125 µg/mL, while essential oil of T. convolutus was found to be effective at concentrations of 250 and 125 µg/mL. A reduction in cell proliferation was observed in colon carcinoma cells (HT-29) treated with 500 µg/mL camphor for 48 h. No statistically significant effect was found in Umbilical Vein Endothelial Cells (HUVEC) treated with essential oil and camphor.

Preparation, carbonic anhydrase enzyme inhibition and antioxidant activity of novel 7-amino-3,4-dihydroquinolin-2(1H)-one derivatives incorporating mono or dipeptide moiety.

New dipeptide-dihydroquinolinone derivatives were successfully synthesised by benzotriazole mediated nucleophilic acyl substitution reaction and their structures were elucidated by spectroscopic and analytic techniques. The carbonic anhydrase (CA, EC 4.2.1.1) inhibitory activity of the new compounds was determined against four human (h) isoforms, hCA I, hCA II, hCA IX and hCA XII. While all compounds showed moderate to good in vitro CA inhibitory properties against hCA IX and hCA XII with inhibition constants in the micromolar level (37.7-86.8 and 2.0-8.6 µM, respectively), they did not show inhibitory activity against hCA I and hCA II up to 100 µM concentration. The antioxidant capacity of the peptide-dihydroquinolinone conjugates was determined using 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical scavenging method. Most of the synthesised compounds showed low antioxidant activities compared to the control antioxidant compounds BHA and α-tocopherol.

Synthesis and human carbonic anhydrase I, II, VA, and XII inhibition with novel amino acid-sulphonamide conjugates.

A series of amino acid-sulphonamide conjugates was prepared through benzotriazole mediated coupling reactions and characterised by 1H-NMR, 13C-NMR, MS, and FTIR spectroscopic techniques as well as elemental analysis. The carbonic anhydrase (CA, EC 4.2.1.1) inhibitory activity of the new compounds was determined against four human (h) isoforms, hCA I, hCA II, hCA VA, and hCA XII. Most of the synthesised compounds showed effective in vitro CA inhibitory properties. The new amino acid-sulphonamide conjugates showed potent inhibitory activity against hCA II, some of them at subnanomolar levels, exhibiting more effective inhibitory activity compared to the standard drug acetazolamide. Some of these sulphonamides were also found to be effective inhibitors of hCA I, hCA VA, and hCA XII, with activity from the low to high nanomolar range.

Synthesis carbonic anhydrase enzyme inhibition and antioxidant activity of novel benzothiazole derivatives incorporating glycine, methionine, alanine, and phenylalanine moieties.

Thirteen novel benzothiazole derivatives incorporating glycine, methionine, alanine, and phenylalanine were synthesised by facile acylation reactions through benzotriazole or DCC mediated reactions and their structures were identified by 1H-NMR, 13C-NMR, and FT-IR spectroscopic techniques and elemental analysis. The carbonic anhydrase (CA, EC 4.2.1.1) inhibitory activity of the new compounds was assessed against four human (h) isoforms, hCA I, hCA II, hCA V, and hCA XIII. Some of the synthesised compounds showed good in vitro carbonic anhydrase inhibitory properties, with inhibition constants in the micromolar level. The new amino acid benzothiazole conjugates found to be more effective against hCA V and hCA II inhibition. In vitro antioxidant activities of the novel compounds were determined by DPPH method. Most of the synthesised compounds showed moderate to low antioxidant activities compared to the control antioxidant compounds (BHA and α-tocopherol).

Synthesis and carbonic anhydrase inhibitory properties of novel 4-(2-aminoethyl)benzenesulfonamide-dipeptide conjugates.

Thirty novel sulfonamide derivatives incorporating dipeptide were synthesized by facile acylation through benzotriazole mediated reactions and their structures were identified by 1H NMR, 13C NMR, MS and FT-IR spectroscopic techniques and elemental analysis. The carbonic anhydrase (CA, EC 4.2.1.1) inhibitory activity of the new compounds was assessed against four human (h) isoforms, hCA I, hCA II, hCA IV and hCA XII. Most of the synthesized compounds showed excellent in vitro carbonic anhydrase inhibitory properties comparable to those of the clinically used drug acetazolamide (AAZ). The new unprotected dipeptide-sulfonamide conjugates showed very effective inhibitory activity, in the low nanomolar range against II and XII, being less effective as hCA I and IV inhibitors. Four of the thirty compounds also showed strong inhibitory activity against hCA XII compared to AAZ.

Synthesis of novel dipeptide sulfonamide conjugates with effective carbonic anhydrase I, II, IX, and XII inhibitory properties.

Twenty-four novel sulfonamide derivatives incorporating dipeptide tails were synthesized by facile acylation reactions of homosulfanilamide through benzotriazole or dicyclohexyl carbodiimide (DCC) mediated coupling reactions. The carbonic anhydrase (CA, EC 4.2.1.1) inhibitory activity of the new compounds was assessed against four human (h) isoforms, hCA I, hCA II, hCA IX and hCA XII. Most of the synthesized compounds showed good in vitro carbonic anhydrase inhibitory properties, with inhibition constants in the low nanomolar range. Particularly, the new dipeptide-sulfonamide conjugates incorporating Ala, Phe and Met in the dipeptide sequence, showed the most effective inhibitory activity against to CA IX and XII.

Synthesis and carbonic anhydrase I, II, IV and XII inhibitory properties of N-protected amino acid - sulfonamide conjugates.

N-protected amino acids (Gly, Ala and Phe protected with Boc and Z groups) were reacted with sulfonamide derivatives, leading to the corresponding N-protected amino acid-sulfonamide conjugates. The carbonic anhydrase (CA, EC 4.2.1.1) inhibitory activity of the new compounds was assessed against four human (h) isoforms, hCA I, hCA II, hCA IV and hCA XII. Among them, hCA II, IV and XII are antiglaucoma drug targets, being involved in aqueous humor secretion within the eye. Low nanomolar inhibition was measured against all four isoforms with the 20 reported sulfonamides, but no selective inhibitory profiles, except for some CA XII-selective derivatives, were observed. hCA I, II and XII were generally better inhibited by sulfonamides incorporating longer scaffolds and Gly/Ala, whereas the best hCA IV inhibitors were homosulfanilamide derivatives, incorporating Phe moieties. The amino acid-sulfonamide conjugates show good water solubility and effective hCA II, IV and XII inhibition, and may be considered as interesting candidates for antiglaucoma studies.

Synthesis and carbonic anhydrase inhibitory properties of amino acid - coumarin/quinolinone conjugates incorporating glycine, alanine and phenylalanine moieties.

N-Protected amino acids (Gly, Ala and Phe) were reacted with amino substituted coumarin and quinolinone derivatives, leading to the corresponding N-protected amino acid-coumarin/quinolinone conjugates. The carbonic anhydrase (CA, EC 4.2.1.1) inhibitory activity of the new compounds was assessed against various human (h) isoforms, such as hCA I, hCA II, hCA IV and hCA XII. The quinolinone conjugates were inactive as enzyme inhibitors, whereas the coumarins were ineffective hCA I/II inhibitors (KIs > 50 µM) but were submicromolar hCA IV and XII inhibitors, with inhibition constants ranging between 92 nM and 1.19 µM for hCA IV, and between 0.11 and 0.79 µM for hCA XII. These coumarin derivatives, as many others reported earlier, thus show an interesting selective inhibitory profile for the membrane-bound over the cytosolic CA isoforms.

Synthesis, characterization and carbonic anhydrase inhibitory activity of novel benzothiazole derivatives.

N-protected amino acids were reacted with substituted benzothiazoles to give the corresponding N-protected amino acid-benzothiazole conjugates (60-89%). Their structures were confirmed by proton nuclear magnetic resonance ((1)H NMR), carbon-13 nuclear magnetic resonance ((13)C NMR), IR and elemental analysis. Their carbonic anhydrase (CA, EC 4.2.1.1) inhibitory activities were determined against two cytosolic human isoforms (hCA I and hCA II), one membrane-associated (hCA IV) and one transmembrane (hCA XII) enzyme by a stopped-flow CO2 hydrase assay method. The new compounds showed rather weak, micromolar inhibitory activity against most of these enzymes.

Macrocyclic peptidomimetics with antimicrobial activity: synthesis, bioassay, and molecular modeling studies.

Novel, cyclic peptidomimetics were synthesized by facile acylation reactions using benzotriazole chemistry. Microbiological testing of the synthesized compounds revealed an exceptionally high activity against Candida albicans with a minimum inhibitory concentration (MIC) two orders of magnitude lower than the MIC of the antifungal reference drug amphotericin B. A strikingly high activity was also observed against three Gram-negative bacterial strains (Pseudomonas aeruginosa, Klebsiella pneumoniae and Proteus vulgaris), two of which are known human pathogens. Thus the discovered chemotype is a potential polypharmacological agent. The toxicity against mammalian tumor cells was found to be low, as demonstrated in five different human cell lines (HeLa, cervical; PC-3, prostate; MCF-7, breast; HepG2, liver; and HCT-116, colon). The internal consistency of the experimental data was studied using 3D-pharmacophore and 2D-QSAR.

Determination of elements by atomic absorption spectrometry in medicinal plants employed to alleviate common cold symptoms.

Eleven important medicinal plants generally used by the people of Turkey for the treatment of common cold have been studied for their mineral contents. Eleven minor and major elements (essential, non-essential and toxic) were identified in the Asplenium adiantum-nigrum L. , Althaea officinalis L. , Verbascum phlomoides L., Euphorbia chamaesyce L., Zizyphus jujube Miller, Peganum harmala L., Arum dioscoridis Sm., Sambucus nigra L., Piperlongum L., Tussilago farfara L. and Elettaria cardamomum Maton by employing flame atomic absorption and emission spectrometry and electro-thermal atomic absorption spectrometry. Microwave digestion procedure for total concentration was applied under optimized conditions for dissolution of medicinal plants. Plant based biological certified reference materials (CRMs) served as standards for quantification. These elements are found to be present in varying concentrations in the studied plants. The baseline data presented in this work can be used in understanding the role of essential, non-essential and toxic elements in nutritive, preventive and therapeutic properties of medicinal plants.

Chemical composition and antimicrobial activity of essential oil of Achillea cretica L. (Asteraceae) from Turkey.

Hydrodistilled volatile oil from the aerial parts of Achillea cretica L. (Asteraceae) was analysed by a combination of GC and GC/MS. Seventy-six components were identified, constituting 86.4% of the oil. The main constituents of the essential oil were caryophylladienol-II (13.4%), ß-maaliene (6.1%), neo-intermedeol (6.0%), carvone (4.9%), spathulenol (4.5%), palmitic acid (3.3%) and selina-3,11-dien-6α-ol (3.2%). The antimicrobial activity was evaluated by the broth-dilution method on nine microbial strains and showed to be quite strong against the Gram-positive bacteria Staphylococcus aureus and Bacillus cereus. The antibacterial properties of A. cretica justify its use in traditional medicine for the treatment of wounds, contaminated through bacterial infections.

Monitoring the effects of water pollution on Cyprinus carpio in Karakaya Dam Lake, Turkey.

Karakaya Dam Lake (KDL) is one of the most important water sources, both for irrigation and fishery, located in eastern part of Turkey. This study is concerned with the pollution of the lake contributed by urban, industrial and agricultural activities. The parameters selected for this aim were the enzymes commonly used as biomarkers of environmental pollution. The activity of glutathione S-transferase (GST), carboxylesterase (CE), lactate dehydrogenase (LDH), acid phosphatase (ACP) and aspartate amino transferase (AST) has been determined in liver tissue samples of Cyprinus carpio, a representative species of KDL. Furthermore, brain acetylcholinesterase (AChE) activity which is mainly affected by pesticides such as organophosphates, has been assayed. Chemical analysis results showed that KDL was polluted by various heavy metals as it was apparent from water, sediment and gill tissue. The activity of brain AChE was significantly lower in all localities than Tecimli area (St-5) where there is no agricultural and industrial activities in the immediate periphery. Thus, this change of AChE activity may relate to agricultural pollution in KDL. On the other hand, no significant differences were found for selected enzyme biomarkers, but condition factor (CF) or hepatosomatic index were significantly different from the St-5 samples, a result that may be attributed to water pollution in KDL by various contaminants.