Designing, synthesis and bioactivities of 4-[3-(4-hydroxyphenyl)-5-aryl-4,5-dihydro-pyrazol-1-yl]benzenesulfonamides.

In this study, 4-[3-(4-hydroxyphenyl)-5-aryl-4,5-dihydro-pyrazol-1-yl]benzenesulfonamide (1-9) types compounds were synthesized and their chemical structures were confirmed by 1H NMR, 13C NMR and HRMS spectra. Cytotoxic and carbonic anhydrase (CA) inhibitory effects of the compounds were investigated. Cytotoxicity experiments pointed out that compound 4, (4-[5-(4-chlorophenyl)-3-(4-hydroxyphenyl)-4,5-dihydro-pyrazol-1-yl]benzenesulfonamide), exerting the highest tumor selectivity (TS) and potency selectivity expression (PSE) values, can be considered as a lead compound of this study in terms of development of novel anticancer agents. All synthesized sulfonamides showed a good inhibition profile on hCA IX and XII in the range of 53.5-923 nM and 6.2-95 nM, respectively. These compounds were 2.5-13.4 times more selective for the inhibition of hCA XII versus hCA IX, except compound 2 which had similar inhibitory action towards both isoenzymes.

Synthesis of 3-aroyl-4-aryl-1-isopropylamino-4-piperidinols and evaluation of the cytotoxicities of the compounds against human hepatoma and breast cancer cell lines.

Some 4-piperidinol derivatives were synthesized and their cytotoxicity was tested against human hepatoma (Huh7) and breast cancer (T47D) cells. Aryl part was changed as phenyl in 2a, 4-methylphenyl in 2b, 4-methoxyphenyl in 2c, 4-chlorophenyl in 2d, 4-fluorophenyl in 2e, 4-bromophenyl in 2f, 4-nitrophenyl in 2g and 2-thienyl in 3. Compounds were synthesized and reported for the first time by this study except 2a and 2d. Chemical structures were confirmed by (1)H NMR, (13)C NMR, IR, MS and elemental analyses. Compounds 2a (3.1 times), 2c (3.8 times), 2f (4.6 times), 2g (1.3 times) and 3 (3.2 times) had 1.3-4.6 times higher cytotoxic potency than the reference compound 5-FU against Huh7 cell line while all the compounds synthesized had shown lower activities against T47D cell line than 5-FU. In the light of these results, compounds 2a, 2c, 2f, 2g and 3 may serve as model compounds for further studies.

GC/MS Evaluation and In Vitro Antioxidant Activity of Essential Oil and Solvent Extracts of an Endemic Plant Used as Folk Remedy in Turkey: Phlomis bourgaei Boiss.

This study was outlined to examine the chemical composition of hydrodistilled essential oil and in vitro antioxidant potentials of the essential oil and different solvent extracts of endemic Phlomis bourgaei Boiss. used as folk remedy in Turkey. The chemical composition of the oil was analyzed by GC and GC-MS, and the predominant components in the oil were found to be ß -caryophyllene (37.37%), (Z)- ß -farnesene (15.88%), and germacrene D (10.97%). Antioxidant potentials of the solvent extracts and the oil were determined by four testing systems including ß -carotene/linoleic acid, DPPH, reducing power, and chelating effect. In ß -carotene/linoleic acid assay, all extracts showed the inhibition of more than 50% at all concentrations. In DPPH, chelating effect, and reducing power test systems, the water extract with 88.68%, 77.45%, and 1.857 (absorbance at 700 nm), respectively, exhibited more excellent activity potential than other extracts (hexane, ethyl acetate and methanol) and the essential oil at 1.0 mg/mL concentration. The amount of the total phenolics and flavonoids was the highest in this extract (139.50 ± 3.98 µ g gallic acid equivalents (GAEs)/mg extract and 22.71 ± 0.05 µ g quercetin equivalents (QEs)/mg extract).

1-(3-aminomethyl-4-hydroxyphenyl)-3-pyridinyl-2-propen-1-ones: a novel group of tumour-selective cytotoxins.

Two series of 1-(3-aminomethyl-4-hydroxyphenyl)-3-pyridinyl-2-propen-1-ones, designed as novel cytotoxins, were synthesized. The compounds had low CC50 values in the micromolar range against HL-60 promyelocytic leukemic cells and HSC-2, HSC-3 and HSC-4 oral squamous cell carcinomas. The CC50 values of these compounds were higher towards non-malignant HGF (gingival fibroblasts), HPC (pulp cells), and HPLF (periodontal ligament fibroblasts) cells, which reveals the tumour-selectivity of these enones. A representative compound 4c caused cleavage of PARP1 in HSC-2 cells but not in HGF cells, which may be a contributing factor to the tumour-selectivity.

Synthesis of some Mannich bases with dimethylamine and their hydrazones and evaluation of their cytotoxicity against Jurkat cells.

1-Aryl-3-dimethylamino-1-propanone hydrochlorides type mono Mannich bases, D series, and corresponding hydrazone derivatives, K series, were synthesized and their cytotoxicity was tested against Jurkat cells (transformed human T-lymphocytes). The aryl part was changed as phenyl in D1 and K1, 4-methylphenyl in D2 and K2, 4-methoxyphenyl in D3 and K3, 4-hydroxyphenyl in D4 and K4, 4-chlorophenyl in D5 and K5, 3-methoxyphenyl in D6 and K6, 4-fluorophenyl in D7 and K7, 4-bromophenyl in D8 and K8, 3-hydroxyphenyl in D9 and K9, and 2-acetylthiophene in D10 and K10. Of the compounds synthesized, K2, K3, K5, K6, K7, K8, K9, and K10 are reported for the first time. Cytotoxic activities of the D and K series were compared with each other to see alterations in bioactivity depending on the chemical structures in Jurkat cells. Cytotoxicities of the compounds synthesized were also compared with the reference compound, 5-fluorouracil (CAS 148-82-3). Mono Mannich bases, D1 (3.60 times), D2 (4.45 times), D3 (2.46 times), D4 (3.52 times), D5 (5.18 times), D6 (3.20 times), D7 (3.23 times), D8 (3.95 times), D9 (3.36 times) and D10 (3.99 times) had 2.46-5.18 times higher cytotoxic potency than the reference compound 5-fluorouracil against Jurkat cells, while hydrazones K1 (4.92 times), K2 (4.65 times), K3 (6.04 times), K4 (6.34 times), K5 (4.67 times), K6 (5.12 times), K7 (5.39 times), K8 (8.31 times), K9 (4.65 times) and K10 (8.65 times) had 4.65-8.65 times higher cytotoxic potency than the reference compound 5-fluorouracil against the same cell line. On the other hand, hydrazone compounds K1 (1.37 times), K3 (2.46 times), K4 (1.80 times), K6 (1.60 times), K7 (1.67 times), K8 (2.11 times), K9 (1.38 times), and K10 (2.17 times) had 1.37-2.46 times higher cytotoxic potency than their corresponding mono Mannich bases. The results of this study suggest that hydrazones were better compounds compared with the corresponding mono Mannich bases in terms of cytotoxicity, and they may serve as model compounds to develop new cytotoxic agents for further studies.

The design and cytotoxic evaluation of some 1-aryl-3-isopropylamino-1-propanone hydrochlorides towards human Huh-7 hepatoma cells.

A series of 1-aryl-3-isopropylamino-1-propanone hydrochlorides 1 and a related heterocyclic analog 2 as candidate antineoplastic agents were prepared and the rationale for designing these compounds is presented. A specific objective in this study is the discovery of novel compounds possessing growth-inhibiting properties of hepatoma cells. The compounds in series 1 and 2 were prepared and their structures established unequivocally. X-ray crystallography of two representative compounds 1d and 1g were achieved. Over half of the compounds are more potent than 5-fluorouracil which is an established drug used in treating liver cancers. QSAR evaluations and molecular modeling studies were undertaken with a view to detecting some physicochemical parameters which govern cytotoxic potencies. A number of guidelines for amplification of the project have been formulated.

Essential oil composition and antioxidant activity of Thymus longicaulis C. Presl subsp. longicaulis var. longicaulis.

This study is designed to examine the chemical composition and in vitro antioxidant activity of the hydrodistillated essential oil and various extracts obtained from Thymus longicaulis subsp. longicaulis var. longicaulis. GC and GC-MS analysis of the essential oil were resulted in determination 22 different compounds, representing 99.61% of total oil. gamma-terpinene, thymol and p-cymene were determined as the major compounds of the oil (27.80, 27.65 and 19.38%, respectively). Antioxidant activities of the samples were determined by four different test systems namely beta-carotene/linoleic acid, DPPH, reducing power and chelating effect. Essential oil showed the highest antioxidant activity in beta-carotene/linoleic acid system among the experiments examined. In the case of other test systems, in general, methanol and water extracts exhibited the strongest activity profiles. Especially, reducing power of water extract was found superior than those of synthetic antioxidants. As well as the antioxidant activities of the extracts, they were evaluated in terms of their total phenolic and flavonoid contents. Hexane and water extracts were found to be rich-in phenolics. However, flavonoids were determined in the highest level in methanol extract.

Antimicrobial activities of essential oil and hexane extract of Florence fennel [Foeniculum vulgare var. azoricum (Mill.) Thell.] against foodborne microorganisms.

The objective of this study was to determine the chemical compositions of the essential oil and hexane extract isolated from the inflorescence, leaf stems, and aerial parts of Florence fennel and the antimicrobial activities of the essential oil, hexane extract, and their major component, anethole, against a large variety of foodborne microorganisms. Gas chromatography and gas chromatography-mass spectrometry analysis showed that the essential oils obtained from inflorescence, leaf stems, and whole aerial parts contained (E)-anethole (59.28-71.69%), limonene (8.30-10.73%), apiole (trace to 9.23%), beta-fenchyl acetate (3.02-4.80%), and perillene (2.16-3.29%) as the main components. Likewise, the hexane extract of the plant sample exhibited a similar chemical composition, and it contained (E)-anethole (53.00%), limonene (27.16%), gamma-terpinene (4.09%), and perillene (3.78%). However, the hexane extract also contained less volatile components such as n-hexadecanoic acid (1.62%), methyl palmitate (1.17%), and linoleic acid (1.15%). The in vitro antimicrobial assays showed that the essential oil, anethole, and hexane extract were effective against most of the foodborne pathogenic, saprophytic, probiotic, and mycotoxigenic microorganisms tested. The results of the present study revealed that (E)-anethole, the main component of Florence fennel essential oil, is responsible for the antimicrobial activity and that the essential oils as well as the hexane extract can be used as a food preservative. This study is the first report showing the antimicrobial activities of essential oil and hexane extract of Florence fennel against probiotic bacteria.

Biological activity of 1-aryl-3-phenethylamino-1-propanone hydrochlorides and 3-aroyl-4-aryl-1-phenethyl-4-piperidinols on PC-3 cells and DNA topoisomerase I enzyme.

A number of studies reported Mannich bases to manifest antimicrobial, cytotoxic, anticancer, anti-inflammatory, and anticonvulsant activities. A considerable number of therapeutically important cytotoxic compounds are active on DNA topoisomerases that regulate the DNA topology. In the present study we evaluated the biological activity of mono-Mannich bases, 1-aryl-3-phenethylamino-1-propanone hydrochlorides (1a-10a), and semicyclic mono-Mannich bases, 3-aroyl-4-aryl-1-phenethyl-4-piperidinols (1b-9b), synthesized in our laboratory. We employed androgen-independent human prostate cancer cells (PC-3) to assess the cytotoxicity of the compounds and extended the biological activity evaluation to cover supercoil relaxation assays of mammalian type I topoisomerases. Our results showed that the compounds had cytotoxicity within the 8.2-32.1 microM range, while two compounds gave rise to a comparable average value in topo I interference of 42% and 40% for 10a (with a hydroxy substituent on the phenyl ring from mono-Mannich bases) and 5b (with a fluoro substituent on the phenyl ring from the semicyclic mono-Mannich base series, piperidinols), respectively.

Chemical composition of hydrodistilled essential oil of Artemisia incana (L.) Druce and antimicrobial activity against foodborne microorganisms.

The oil obtained by hydrodistillation from the aerial parts of Artemisia incana (L.) Druce from Turkey was analyzed by GC and GC/MS. Sixty-three compounds were characterized, representing 97.2% of the total components detected, and camphor (19.0%), borneol (18.9%), 1,8-cineole (14.5%), bornyl acetate (7.8%), camphene (4.9%), and alpha-thujone (4.8%) were identified as predominant components. The essential oil was also tested for its antimicrobial activity against 44 different foodborne microorganisms, including 26 bacteria, 15 fungi, and 3 yeast species. The essential oil of A. incana exhibited considerable inhibitory effects against all bacteria, fungi, and yeast species tested. However, the oil showed lower inhibitory activity against the tested bacteria than the reference antibiotics.

Cytotoxicity of 1-aryl-3-buthylamino-1-propanone hydrochlorides against Jurkat and L6 cells.

1-Aryl-3-buthylamino-1-propanone hydrochloride type mono Mannich bases were synthesized and their cytotoxicity was tested against transformed human T-lymphocytes (Jurkat cells) and rat skeletal muscle derived myoblasts (L6 cells). Aryl part was changed as phenyl in 1, 4-methylphenyl in 2, 4-chlorophenyl in 3, 4-fluorophenyl in 4, 4-bromophenyl in 5, 4-hydroxyphenyl in 6, 2-acethylthiophene in 7. Of the compounds synthesized, 2, 5, 6, and 7 are reported for the first time. Compounds 1-7 had 3.16, 3.13, 3.35, 2.87, 4.17, 2.60, and 3.04 times higher cytotoxic potency than the reference compound 5-fluorouracil (CAS 51-21-8) against Jurkat cells, respectively. Compounds 1, 3, 4, 5, 6, and 7 had 1.22, 1.46, 1.59, 2.18, 1.24, and 1.45 times higher cytotoxic potency than the reference compound 5-fluorouracil against L6 cells, respectively. Among the compounds tested, only compound 5 had almost equal cytotoxic potency with the reference compound melphalan (CAS 148-82-3) against Jurkat and L6 cells. All compounds synthesized showed higher cytotoxic activity against Jurkat cells compared with L6 cells. Specifically, compounds 1-7 had 2.05, 2.68, 1.82, 1.43, 1.51, 1.66, and 1.66 times higher cytotoxicity against Jurkat cells compared with L6 cells. In Jurkat cells, there was a significant negative correlation between Log P and IC50 values (correlation coefficient: -0.955, p = 0.03), which actually means a positive correlation between the Log P and the cytotoxic activity of the compounds. These results suggest that the most potent compound 5 (a 4-bromo derivative) against both cell lines may serve as a model compound to develop new cytotoxic agents for further studies.

Studies on the antioxidant activity of essential oil and different solvent extracts of Vitexagnuscastus L. fruits from Turkey.

This study is designed to examine the chemical composition and antioxidant activity of the essential oil and different solvent extracts of Vitexagnuscastus. GC and GC-MS analysis was resulted in the detection of 27 components, representing 94.5% of the oil. Major components of the oil were 1,8-cineole (24.98%), sabinene (13.45%), alpha-pinene (10.60%), alpha-terpinyl acetate (6.66%), and (Z)-beta-farnesene (5.40%). Antioxidant activities of the samples were determined by three different test systems, DPPH, beta-carotene/linoleic acid and reducing power assays. In all systems, water extract exhibited excellent activity potential than those of other extracts (hexane, dichloromethane, ethyl acetate and methanol) and the oil. As expected, amount of total phenolics was very high in this extract (112.46+/-1.22mugGAEs/mgextract). Dichloromethane extract has been found to be rich in flavonoids. A positive correlation was observed between the antioxidant activity potential and total phenolic and flavonoid levels of the extracts.

Antifungal, phytotoxic and insecticidal properties of essential oil isolated from Turkish Origanum acutidens and its three components, carvacrol, thymol and p-cymene.

The chemical composition of essential oil isolated by hydrodistillation from the aerial parts of Origanum acutidens was analyzed by GC-MS. Carvacrol (87.0%), p-cymene (2.0%), linalool acetate (1.7%), borneol (1.6%) and beta-caryophyllene (1.3%) were found to be as main constituents. Antifungal, phytotoxic and insecticidal activities of the oil and its aromatic monoterpene constituents, carvacrol, p-cymene and thymol were also determined. The antifungal assays showed that O. acutidens oil, carvacrol and thymol completely inhibited mycelial growth of 17 phytopathogenic fungi and their antifungal effects were higher than commercial fungicide, benomyl. However, p-cymene possessed lower antifungal activity. The oil, carvacrol and thymol completely inhibited the seed germination and seedling growth of Amaranthus retroflexus, Chenopodium album and Rumex crispus and also showed a potent phytotoxic effect against these plants. However, p-cymene did not show any phytotoxic effect. Furthermore, O. acutidens oil showed 68.3% and 36.7% mortality against Sitophilus granarius and Tribolium confusum adults, respectively. The findings of the present study suggest that antifungal and herbicidal properties of the oil can be attributed to its major component, carvacrol, and these agents have a potential to be used as fungicide, herbicide as well as insecticide.