Phosphorus-Nitrogen Compounds: Part 76. Design and Syntheses of Dispiro- and Trispiro(N/N)cyclotriphosphazenes: Conformational and Structural Analyses, Chirality, Electrochemical, Dye-Sensitized Solar Cells, and Bioactivity Studies.

The reactions of monospirocyclotriphosphazenes (1 and 2) with N-methyl-1,3-diaminopropane gave unsymmetrical cis-(3 and 5) and trans-(4 and 6) dispirocyclotriphosphazenes. Trans-cis-trans (tct) (7 and 11), cis-cis-cis (ccc) (8 and 12), trans-trans-cis (ttc) (9 and 13), and cis-trans-trans (ctt) (14) trispirocyclotriphosphazenes were obtained from the reactions of 3 and 5 and 4 and 6 with N-methyl-1,3-diaminopropane. cis-Dispirocyclotriphosphazenes (3 and 5) exist as "pseudomesoracemates", while trans-dispirocyclotriphosphazenes (4 and 6) are in "racemates". The existences of cis-3 and trans-4 as "pseudomesoracemate" and "racemate" were confirmed by 31P NMR spectra recorded by the addition of "chiral solvating agent (CSA)". X-ray crystallography proved that the absolute configurations of each enantiomer of cis-5 and trans-6 are SS' and RS'. Trispirocyclotriphosphazenes tct, ttc, ccc, and ctt exist as racemates, pseudomesoracemate, and meso forms. Furthermore, Hirshfeld surface analysis of the crystal structures of cis-5 and trans-6 revealed that the most significant contribution to crystal packing comes from H···H (58.2 and 57.6%, respectively). An oxidation-reduction wave was detected in the reversible cyclic voltammograms of the phosphazenes. The highest power conversion efficiency in dye-sensitized solar cell studies was obtained with cis-5. Additionally, trans-6 exhibited the lowest minimal inhibitory concentration value (78.1 µM) against Candida tropicalis, and it was observed to cleave pBR322 plasmid DNA.

PDCD4 and MIR-21 are promising biomarkers in the follow-up of OED in liquid biopsies.

This research aims to examine the impact of programmed cell death 4 (PDCD4), microRNA-21 (miR-21) and microRNA-208a (miR-208a) transcripts, and protein levels on oral epithelial dysplasia (OED) development in oral squamous cell carcinoma (OSCC). METHODS: The research investigation involved the collection of saliva, blood, and tissue samples from a total of 20 patients diagnosed with OSCC, 15 patients diagnosed with OED, and 15 healthy individuals. PDCD4, miR-21, and miR-208a expression was performed by quantitative reverse transcription polymerase chain reaction (qRT-PCR). PDCD4 protein levels were assessed using enzyme-linked immunosorbent assay (ELISA) in both saliva and blood samples. For statistical analysis, the Kruskal-Wallis test and the Spearmen rank test were utilised. RESULTS: PDCD4 expression levels were considerably lower in patients with OSCC and OED (p < 0.05) in three biological samples. In contrast, miR-21 expression was higher in OED and OSCC patients. Patients with low PDCD4 mRNA levels and strong miR-21 expression had a significant connection (p < 0.05) with tumor size and depth. CONCLUSIONS: Examining PDCD4 and miR-21 transcript levels may help detect the transition from OED to OSCC. This work suggests that PDCD4 and miR-21 expression levels in liquid biopsies may be biomarkers for OED monitoring in the future.

Phosphorus-nitrogen compounds: part 53-synthesis, characterization, cytotoxic and antimicrobial activity, DNA interaction and molecular docking studies of new mono- and dispirocyclotriphosphazenes with pendant arm(s).

Mono-/dispirocyclotriphosphazenes with pendant arm(s) are robust, but they are less investigated inorganic ring systems. In this study, a series of mono (3 and 4)- and dispirocyclotriphosphazenes with 4-chloro-benzyl pendant arm(s) (13-16) was obtained from the Cl exchange reactions of hexachlorocyclotriphosphazene with sodium (N-benzyl)aminopropanoxides (1 and 2). When compound (3) reacted with excess pyrrolidine, morpholine, tetra-1,4-dioxa-8-azaspiro[4,5]decane (DASD) and piperidine, the fully substituted monospirocyclotriphosphazenes (7, 9, 10 and 12) occurred. But, the reactions of 4 with excess piperidine and morpholine produced the gem-piperidino (5)- and morpholino (6)-substituted monospirocyclotriphosphazenes, whereas the reactions of 4 with excess pyrrolidine and DASD gave the fully substituted monospirocyclotriphosphazenes (8) and (11). However, it should be indicated that these derivatives were obtained to be used for the investigation of their spectral, stereogenic and biological properties. The structures of 5, 7 and 14 were determined crystallographically. X-ray data of 5 and 14 displayed that both of compounds were chiral in solid state, and their absolute configurations were assigned as R and RR. Additionally, the antimicrobial activities of phosphazenes were investigated. Minimum inhibitory concentrations, minimal bacterial concentrations and minimum fungicidal concentrations of phosphazenes were determined. The interactions of phosphazenes with plasmid DNA were evaluated by agarose gel electrophoresis. The cytotoxic activities of compounds were studied against L929 fibroblast and DLD-1 colon cancer cells. In addition, density functional theory calculations of 5, 7 and 14 were reported, and their molecular docking studies with DNA, E. coli DNA gyrase and topoisomerase IV were presented.

Synthesis, characterization and DNA binding studies of platinum(II) complexes with benzimidazole derivative ligands.

The aim of this study was to synthesize and evaluate plasmid DNA interaction of new platinum(II) complexes with some 2-substituted benzimidazole derivatives as carrier ligands which may have potent anticancer activity and low toxicity. Twelve benzimidazole derivatives carrying indole, 2-/or 3-/or 4-methoxyphenyl, 4-methylphenyl, 3,4-dimethoxyphenyl, 3,4,5-trimethoxyphenyl, 4-methoxybenzyl, 3,4,5-trimethoxybenzyl, 3,4,5-trimethoxystyryl, 3,4,5-trimethoxybenzylthio or dimethylamino ethyl groups in their position 2 and twelve platinum(II) complexes with these carrier ligands were synthesized. The chemical structure of the platinum complexes have been characterized by their elemental analysis and FIR, 1H NMR and mass spectra and their 1H NMR and FIR spectra were interpreted by comparison with those of the ligands. The interaction of all the ligands and their complexes with plasmid DNA and their restriction endonuclease reactions by BamHI and HindIII enzymes were studied by agarose gel electrophoresis. It was determined that complex 1 [dichloro-di(2-(1H-indole-3-yl)benzimidazole)platinum(II)·2H2O] has stronger interaction than carboplatin and complex 10 [dichloro-di(2-(3,4,5-trimethoxystyryl)benzimidazole)platinum(II)·2H2O] has stronger interaction than both carboplatin and cisplatin with plasmid DNA.

Investigation of glucocorticoid receptor and calpain-10 gene polymorphisms in Turkish patients with type 2 diabetes mellitus

Background/aim: We proposed to investigate the role of calpain-10 (CAPN10) gene single nucleotide polymorphism (SNP)-19 and SNP-44 and glucocorticoid receptor (NR3C1) gene N363S polymorphisms in Turkish patients with type 2 diabetes mellitus (T2DM).Materials and methods: Peripheral blood samples were obtained from 125 patients with T2DM and 112 healthy volunteers. Genotyping was carried out by the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method. Results: There were no statistically significant differences found between the allele and genotype frequencies of CAPN10 SNP-19, CAPN10 SNP-44, and NR3C1 N363S polymorphisms and T2DM development (P > 0.05). The CAPN10 SNP-19 del-allele, CAPN10 SNP-44 C-allele, and NR3C1 N363S G-allele were determined to be risk factors for T2DM development. In T2DM patients an association was identified between the CAPN10 SNP-19 del-allele, homozygous del/del genotype, SNP-44 C-allele, heterozygous TC genotype, NR3C1 N363S G-allele, heterozygous AG genotype, and increased BMI. Conclusion: The present study demonstrates that the SNP-44 polymorphism is associated with T2DM susceptibility and contributes to the risk of T2DM.

Phosphorus-nitrogen compounds: part 30. Syntheses and structural investigations, antimicrobial and cytotoxic activities and DNA interactions of vanillinato-substituted NN or NO spirocyclic monoferrocenyl cyclotriphosphazenes.

The gradual Cl replacement reactions of NN (1-3) or NO spirocyclic monoferrocenyl cyclotriphosphazenes (4 and 5) with the potassium salt of 4-hydroxy-3-methoxybenzaldehyde (potassium vanillinate) resulted in the mono (1a-5a), geminal (gem-1b-5b), non-geminal (cis-5b and trans -1b-4b), tri (1c, 3c-5c) and tetra-vanillinato-substituted phosphazenes (1d-5d). All the phosphazene derivatives have stereogenic P-center(s), except tetra-substituted ones. The vanillinatophosphazenes have reversible voltammograms with one-electron anodic and cathodic peaks which are attributed to ferrocenyl redox probe. The structures of the new phosphazene compounds were determined by FTIR, MS, (1)H, (13)C{(1)H} and (31)P{(1)H} NMR spectral data. The solid-state structure of cis -5b was examined by single-crystal X-ray diffraction techniques. In addition, the compounds were tested in HeLa cancer cell lines using MTT assay. The 12 phosphazene derivatives were screened for antimicrobial activity, and 3c was very effective against S. aureus even at 4.88 µM concentration, taking into account the MIC values. Besides, interactions between the phosphazenes and pBR322 plasmid DNA were also investigated.

NAMPT, IL-6, and vaspin gene expressions and serum protein levels in type 2 diabetes mellitus and related complication.

Background/aim: Type 2 diabetes mellitus (T2DM) is the most common type of diabetes and occurs due to insufficient insulin secretion or inability to use existing insulin and the effects of environmental factors. Although there are many studies on the pathophysiology of T2DM, the mechanisms contributing to the pathogenesis of insulin resistance and pancreatic beta-cell dysfunction have not been completely elucidated. Some adipokines secreted from adipose tissue, which are the primary regulators of insulin resistance, affect immune and inflammatory functions. Altered adipokine profiles have been observed in obesity and T2DM, leading to severe metabolic risks and changes in insulin sensitivity. Materials and methods: This study used quantitative PCR and ELISA techniques to analyze samples from individuals without diabetes (control group) and with T2DM (macrovascular and microvascular complications and without complications) for at least 10 years. Results: The mRNA expression and protein levels of NAMPT, IL-6, and vaspin genes were determined. While there was no significant difference in NAMPT, IL-6, and vaspin mRNA expression levels between diabetic groups, there was a significant decrease between the patient and control groups (p < 0.001). For serum protein levels, NAMPT protein levels decreased significantly in the uncomplicated group, while IL-6 and vaspin protein levels increased significantly in both microvascular and macrovascular complication groups (p < 0.001). Conclusion: The correlations between gene expressions, clinical parameters, and protein levels are crucial to understanding the implications of the findings.

Antibacterial efficacy of silver nanoparticles, sodium hypochlorite, chlorhexidine, and hypochlorous acid on dentinal surfaces infected with Enterococcus faecalis.

The purpose of this study was to evaluate the antibacterial effect of silver nanoparticles (AgNPs) against Enterococcus faecalis and compare it with different irrigation solutions. This study was performed using 64 dentin blocks. E. faecalis suspension was dispensed to each sample and incubated under anaerobic conditions at 37°C throughout 21 days. After the inoculation period, the following solutions were added to each group and kept for 5 min: Group 1, 5.25% sodium hypochlorite (NaOCl); Group 2, 2.5% NaOCl; Group 3, 1% NaOCl; Group 4, 2% chlorhexidine (CHX); Group 5, 200 ppm hypochlorous acid (HOCl); and Group 6, AgNPs. The samples of positive control were treated with sterile saline. Biofilm viability assay was performed using the LIVE/DEAD BacLight Bacterial Viability Kit. Samples were examined using confocal laser scanning microscopy, respectively. There was no significant difference between the 5.25% NaOCl, 2.5% NaOCl, and 1%NaOCl groups (p > .05). However, these groups showed statistically higher antibacterial activity than the 2% CHX, 200 ppm HOCl, and AgNP groups. Also, 2% CHX showed greater percentage of dead cells compared with the AgNP and HOCl groups. While AgNPs group showed lower dead cell rate than all NaOCl groups and 2% CHX, it caused higher dead cells than 200 ppm HOCl group. The 200 ppm HOCl group showed the lowest percentage of dead cells (p < .05) Although the antibacterial effect of AgNPs is not as high as NaOCl and CHX, it has considerable bactericidal activity against E. faecalis and can be improved by further studies. RESEARCH HIGHLIGHTS: New antimicrobial approaches for root canal irrigation. Antimicrobial effect of silver nanoparticles against E. faecalis. Elimination of the biofilm layer for the success of endodontic treatment.

Phosphorus-nitrogen compounds. Part 58. Syntheses, structural characterizations and biological activities of 4-fluorobenzyl-spiro(N/O)cyclotriphosphazene derivatives.

The starting compound, tetrachloro-4-fluorobenzyl-spiro(N/O)cyclotriphosphazene (2), was synthesized from the substitution reaction of hexachlorocyclotriphosphazatriene (N3P3Cl6; trimer; HCCP) with sodium 3-(4-fluorobenzylamino)-1-propanoxide (1). Reactions of spiro (2) with excess 1-(2-aminoethyl)-piperidine, 4-(2-aminoethyl)-morpholine, 1-(2-hydroxyethyl)piperidine and 4-(2-aminoethyl)morpholine yielded the fully substituted cyclotriphosphazene derivatives (2a-2d), respectively. Elemental analysis, mass spectrometry (ESI-MS), FTIR, 1H-, 13C- and 31P-NMR data confirmed the structure of the new cyclotriphosphazenes (2a-2d); and the crystal structure of 2 was also identified by X-ray crystallography. The quantum mechanical DFT calculations of 2 were performed to estimate the geometry optimization, total energy, orientation of frontier molecular orbitals (HOMOs and LUMOs), and chemical parameters. In addition, antibacterial and antifungal activities of the fully substituted 4-fluorobenzyl-spiro(N/O)cyclotriphosphazenes (2a-2d) were investigated against G(+) and G(-) bacteria and fungi. Using agarose gel electrophoresis, the DNA cleavage activities of these phosphazenes on double-stranded plasmid DNA were evaluated. To evaluate the abilities of compounds 2a-2d to inhibit cell proliferation in different concentrations, the antiproliferative and antimigrative activities against prostate adenocarcinoma (PC3), breast cancer (MCF7) and colon cancer (HT29) cell lines were studied in vitro; and the compound 2c was determined to be the most efficient against the three cancer cells.Communicated by Ramaswamy H. Sarma.

Phosphorus-nitrogen compounds. Part 24. Syntheses, crystal structures, spectroscopic and stereogenic properties, biological activities, and DNA interactions of novel spiro-ansa-spiro- and ansa-spiro-ansa-cyclotetraphosphazenes.

The reactions of octachlorocyclotetraphosphazene, N(4)P(4)Cl(8), with N(2)O(2) donor-type aminopodands (1a, 1b, 1g, and 1h) afforded two kinds of derivatives, namely, spiro-ansa-spiro (sas) (2a, 2b, 2g, and 2h) and ansa-spiro-ansa (asa) (3a and 3b) phosphazenes. The partly substituted sas phosphazenes (2a and 2b) reacted with excess pyrrolidine and morpholine in tetrahydrofuran to produce the tetrapyrrolidino (2c and 2d) and morpholino (2e and 2f) derivatives. The reactions of the asa phosphazenes (3a and 3b) with excess pyrrolidine and morpholine produced gem-2-trans-6-dichloropyrrolidinophosphazenes (3c and 3d) and -morpholinophosphazenes (3e and 3f). However, the fully substituted products were not obtained in these solvents. In addition, the expected fully substituted compound was not obtained from the reaction of 3a with excess pyrrolidine by standard or microwave-assisted methods. The reaction of the long-chain starting compound (1g) with N(4)P(4)Cl(8) gave sas (2g) and the interesting 2,6-ansa-spiro-bicyclo product (bicyclo-2,6-as; 4g), while the reaction of 1h with N(4)P(4)Cl(8) yielded only sas (2h). The structural investigations of the compounds were verified by elemental analyses, mass spectrometry, Fourier transform infrared, and DEPT, HSQC, HMBC, (1)H, (13)C, and (31)P NMR techniques. The crystal structures of 2b, 3a, 3b, 3e, and 4g were determined by X-ray crystallography. Compounds 2a-2h, 3a-3f, and 4g had two stereogenic P atoms. Compound 3b had one enantiomer according to the Flack parameter, and 3f was a racemic mixture, as shown by chiral high-performance liquid chromatography and chiral-solvating-agent, (R)-(+)-2,2,2-trifluoro-1-(9'-anthryl)ethanol, experiments. Furthermore, compounds 2a, 2c, and 2d exhibited weak antibacterial activity against (G+) bacterium, and 3c and 3d displayed moderate antifungal activity against Candida tropicalis. Gel electrophoresis data demonstrated that 2e, 3c, and 3e promoted the formation of DNA cleavage. The prevention of BamHI digestion by 2a-2f and 3a-3f, except 2b and 2e, disclosed binding with GG nucleotides in DNA.

Cytotoxicity and DNA interactions of some platinum(II) complexes with substituted benzimidazole ligands.

In the present study, four Pt(II) complexes with 2-ethyl (1)/or benzyl (2)/or p-chlorobenzyl (3)/or 2-phenoxymethyl (4) benzimidazole carrier ligands were evaluated for their in vitro cytotoxic activities against the human HeLa cervix, oestrogen receptor-positive MCF-7 breast, and oestrogen receptor-negative MDA-MB 231 breast cancer cell lines. The plasmid DNA interactions and inhibition of the BamHI restriction enzyme activities of the complexes were also studied. Complex 3 was found to be more active than carboplatin for all examined cell lines and comparable with cisplatin, except for the HeLa cell line.

Synthesis of some novel thiocyanotopurine derivatives and investigation of their antimicrobial activity and DNA interactions.

A series of 6-thiocyanatopurine derivatives introduced with different alkyl groups in position 9 was synthesized. The structures of the synthesized compounds were evaluated via spectroscopic methods and elemental methods of analyses. All the synthesized compounds were screened for their antibacterial activities against Gram-positive and Gram-negative bacteria and for their antifungal activities against yeast strains. All the synthesized compounds showed better antibacterial activities against Gram-positive bacteria compared to Gram-negative bacteria. DNA interactions with pBR322 DNA were determined. Most of the compounds caused conformational changes in DNA.

Comparative evaluation of the antifungal efficacy of sodium hypochlorite, chlorhexidine, and silver nanoparticles against Candida albicans.

Candida albicans is a microorganism that causes root canal infections. However, it cannot be eliminated with conventional irrigation solutions. Recently, silver nanoparticles (AgNPs) have become popular for their superior antimicrobial effects. The purpose of this study was to evaluate the antifungal effect of AgNPs to C. albicans comparing with 5.25% sodium hypochlorite (NaOCl) and 2% chlorhexidine (CHX). Silver nanoparticles were synthesized by chemical reduction method. Minimum inhibitory concentration and minimum fungicidal concentration of AgNPs against C. albicans strain were determined according to microdilution method reported by Clinical Laboratory Standards Institute. C. albicans biofilm layer was formed on the dentin blocks for 10 days. The biofilm structure was observed by scanning electron microscopy. Statistical analysis was performed with one way analysis of variance analysis and group comparisons were performed with Tukey test. AgNPs showed the highest antifungal effect among the groups. 5.25% NaOCl showed the lowest antifungal effect among the groups. While the 2% CHX solution had a statistically lower antifungal effect than AgNPs, it was found to have a higher effect than NaOCl (p < .016). Nanoparticles present a wide research field as an alternative irrigation solution in root canal treatment. The antifungal effect of AgNPs against C. albicans was confirmed in this study. Further in vivo studies should evaluate the conditions of use and long-term prognosis of AgNPs.

Phosphorus-nitrogen compounds. 21. Syntheses, structural investigations, biological activities, and DNA interactions of new N/O spirocyclic phosphazene derivatives. The NMR behaviors of chiral phosphazenes with stereogenic centers upon the addition of chiral solvating agents.

The reactions of hexachlorocyclotriphosphazatriene, N(3)P(3)Cl(6), with N/O-donor-type N-alkyl (or aryl)-o-hydroxybenzylamines (1a-1e) produce mono- (2a-2e), di- (3a-3d), and tri- (4a and 4b) spirocyclic phosphazenes. The tetrapyrrolidino monospirocyclic phosphazenes (2f-2i) are prepared from the reactions of partly substituted compounds (2a-2d) with excess pyrrolidine. The dispirodipyrrolidinophosphazenes (3e-3h) and trispirophosphazenes (3i-3k) are obtained from the reactions of trans-dispirophosphazenes with excess pyrrolidine and sodium (3-amino-1-propanoxide), respectively. Compounds 3a-3d have cis and trans geometric isomers. Only the trans isomers of these compounds are isolated. Compounds 3a-3h have two stereogenic P atoms. They are expected to be in cis (meso) and trans (racemic) geometric isomers. In the trans trispiro compounds (3i-3k), there are three stereogenic P atoms. They are expected to be in racemic mixtures. The stereogenic properties of 3a-3k are confirmed by (31)P NMR spectroscopy upon the addition of the chiral solvating agent; (S)-(+)-2,2,2-trifluoro-1-(9'-anthryl)ethanol. The molecular structures of 3i-3k, 4a, and 4b look similar to a propeller, where the chemical environment of one P atom is different from that of others. Additionally, 4a and 4b are also expected to exist as cis-trans-trans and cis-cis-cis geometric isomers, but both of them are found to be in cis-trans-trans geometries. The solid-state structures of 2a, 2e, 2f, 3e, and 3f are determined by X-ray crystallography. The compounds 2f-2i, 3e-3i, and 3k are screened for antibacterial activity against gram-positive and gram-negative bacteria and for antifungal activity against yeast strains. These compounds (except 3f) have shown a strong affinity against most of the bacteria. Minimum inhibitory concentrations (MIC) are determined for 2f-2i, 3e-3i, and 3k. DNA binding and the nature of interaction with pUC18 plasmid DNA are studied. The compounds 2f-2i, 3e-3i, and 3k induce changes on the DNA mobility. The prevention of BamHI and HindIII digestion (except 2g) with compounds indicates that the compounds bind with nucleotides in DNA.

Synthesis and spectroscopic properties of (N/O) mono- and dispirocyclotriphosphazene derivatives with benzyl pendant arms: study of biological activity.

The Cl replacement reactions of hexachlorocyclotriphosphazene (trimer; N 3 P 3 Cl 6 ) with sodium (N-benzyl)- aminopropanoxides (1 and 2) produced monospiro- (3 and 4), cis-, and trans-dispirocyclotriphosphazenes (13-16). The monospiro tetrakis-aminocyclotriphosphazenes (5-12) were obtained by the Cl substitutions of 3 and 4 with different secondary amines. The cis- (13 and 14) and trans-dispirophosphazenes (15 and 16) possessed 2 chiral P centers, and they were able to present meso and racemic forms, respectively. Moreover, the structures of compounds 5 and 14 were designated using X-ray data. The absolute configuration of compound 14 was found as SR in the solid state. Analytical and spectroscopic data of the phosphazenes were consistent with their suggested structures. Antimicrobial activities of the benzyl-pendant-armed cyclotriphosphazenes were scrutinized against G(+) and G(-) bacteria and yeast strains. The bacterium most affected by the synthesized compounds was Pseudomonas aeruginosa . Minimum inhibitory concentrations and minimal bacterial concentrations were in the range of 125-500 µM. Interactions between the phosphazenes (3-12 and 15) and plasmid DNA were studied with agarose gel electrophoresis. The phosphazene- DNA interaction studies of the cyclotriphosphazenes revealed that phosphazenes 3, 4, and 15 had a substantial effect on supercoiled DNA by cleavage of the double helix.

Phosphorus-nitrogen compounds. 18. Syntheses, stereogenic properties, structural and electrochemical investigations, biological activities, and DNA interactions of new spirocyclic mono- and bisferrocenylphosphazene derivatives.

The reactions of hexachlorocyclotriphosphazatriene, N(3)P(3)Cl(6), with mono- (1 and 2) and bisferrocenyldiamines (3-5), FcCH(2)NH(CH(2))(n)NHR(1) (R(1) = H or FcCH(2)-), produce mono- (6 and 7) and spirocyclic bisferrocenylphosphazenes (8-10). The fully substituted phosphazenes (11-15 and 18-21) are obtained from the reactions of corresponding partly substituted phosphazenes (6-10) with excess pyrrolidine and NH(2)(CH(2))(3)ONa, respectively. The reactions of 6 with 1-aza-12-crown-4 afford geminal (16) and tris (17) crown ether-substituted phosphazenes. The structural investigations of the compounds have been verified by elemental analyses, mass spectrometry, Fourier transform IR, (1)H, (13)C, and (31)P NMR, and DEPT, COSY, HETCOR, and HMBC techniques. The crystal structures of 7, 10, 11, and 15 have been determined by X-ray crystallography. In 16 and 17, there are one and two stereogenic P atoms, respectively, and they are expected to be in enantiomeric mixtures. The structures of 18-21 look similar to a propeller. In 20 and 21, there are two stereogenic P atoms, and they exist as cis (meso; 20a and 21a) and trans (racemic; 20b and 21b) geometric isomers, according to the chiral solvating agent (S)-(+)-2,2,2-trifluoro-1-(9'-anthryl)ethanol experiments. Moreover, the compounds 18 and 19 have three stereogenic P atoms, and they exist as enantiomeric mixtures. Cyclic voltammetric investigations of compounds 6-21a reveal that ferrocene redox centers undergo oxidation concurrently at the same potential with basically reversible peaks, and these compounds appear to be quite robust electrochemically. The compounds 11-15 have been screened for antibacterial activity against gram positive and gram negative bacteria and for antifungal activity against yeast strains.The compounds 11, 12, 14, and 15 are evaluated for antituberculosis activity against reference strain Mycobacterium tuberculosis H37Rv (ATCC 27294). Interactions between compounds 11-15 and pBR322 plasmid DNA are studied by agarose gel electrophoresis. These compounds induce conformational changes in the DNA helix.

DNA cleavage, antimicrobial studies and a DFT-based QSAR study of new antimony(III) complexes as glutathione reductase inhibitor.

New antimony(III) complexes, [Sb(2-aminopyridine)2Cl3] (1a), [Sb(2-aminopyridine)2Br3] (1b), [Sb(5-methyl-2-aminopyridine)2Cl3] (2a), [Sb(5-methyl-2-aminopyridine)2Br3] (2b), [Sb(2-aminopyrimidine)2Cl3] (3a), [Sb(2-aminopyrimidine)2Br3] (3b), [Sb(4,6-dimethoxy-2-aminopyrimidine)2Cl3] (4a), [Sb(4,6-dimethoxy-2-aminopyrimidine)2Br3] (4b), [Sb(2-amino-1,3,5-triazine)2Cl3] (5a), [Sb(2-amino-1,3,5-triazine)2Br3] (5b), [Sb(2-guanidinobenzimidazole) Cl3] (6a), [Sb(2-guanidinobenzimidazole)Br3] (6b) [Sb(2- benzyl-2-thiopseudeourea)2Cl3] (7a) and [Sb(2- benzyl-2-thiopseudeourea)2Br3] (7b) were synthesized. Their structures were characterized by elemental analysis, molecular conductivity, FT-IR, (1)H NMR, LC-MS techniques. Glutathione reductase inhibitor activity, antimicrobial activity and DNA cleavage studies of the complexes were determined. The geometrical structures of the complexes were optimized by DFT/B3LYP method with LANL2DZ as basis set. Calculation results indicated that the equilibrium geometries of all complexes have square pyramidal shape. About 350 molecular descriptors (constitutional, topological, geometrical, electrostatic and quantum chemical parameters) of the complexes were calculated by DFT/B3LYP/LANL2DZ method with CODESSA software. Calculated molecular parameters were correlated to glutathione reductase inhibitory activity values (pIC50) of all complexes by Best Multi-Linear Regression (BMLR) method. Obtained two-parameter QSAR equation shows that increase in "maximum partial charge for a H atom" and decrease in HOMO-LUMO gap would be favorable for the glutathione reductase inhibitory activity.

In vitro anti-oxidant, cytotoxic and pro-apoptotic effects of Achillea teretifolia Willd extracts on human prostate cancer cell lines.

BACKGROUND: The majority of Achillea species are the most important native economic plants of Anatolia. They include highly bioactive compounds, so they have therapeutic applications. OBJECTIVE: In the present study, the aim was to investigate in vitro anti-oxidant, cytotoxic and pro-apoptotic effects of Achillea teretifolia Willd extracts (Turkish name: Beyaz civanperÇemi). MATERIALS AND METHODS: The anti-oxidant potential of the extracts was analyzed by the free radical 1,1-diphenyl-2-picryl-hydrazyl (DPPH) and total phenolic content methods. 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay was used to detect cytotoxicity of the extracts onhuman prostate cancer cell lines (DU145 and PC-3) and human gingival fibroblast (HGF) cells. mRNA expression levels of pro-apoptotic (bax, caspase-3) and anti-apoptotic (bcl-2) genes were measured by quantitative real-time polymerase chain reaction. RESULTS: The results showed that extracts exhibited a remarkable DPPH scavenging activity, and total phenolic content of the methanol extract was higher than that of the water extract. As time and concentration were increased, the methanol extract exhibited a more powerful cytotoxic effect on prostate cancer cells. In prostate cancer cells, the levels of mRNA expression of the bax and caspase-3 genes were significantly up-regulated (P < 0.05), whereas the expression of bcl-2 was down-regulated (P < 0.05). In HGF cells, there were no cytotoxic effect and apoptosis induction triggered by the extracts. CONCLUSION: The methanol extract had more powerful anti-oxidant, cytotoxic and pro-apoptotic effects than the water extract. The extracts could be good anti-oxidant sources, and they might include anti-cancer compounds triggering the cytotoxicity and the apoptosis on prostate cancer cells.

Induced of plastid mutations in soybean plant (Glycine max L. Merrill) with gamma radiation and determination with RAPD.

The aim of our study was to induce with radiation of atrazine resistant and tolerated mutants in Coles, Amsoy-71 and 1937 soybean varieties. Atrazine that is photosynthetic inhibitor is the most important herbicide of S-triazin group, and shows toxic effect on soybean plant. For the improvement of the atrazine resistant plants with mutation breeding, the seeds belonging to the three varieties were irradiated with 200 Gy of gamma radiation dose. The irradiated seeds were sown in the field and at the end of harvesting season, every pod at node situated on the main stem was picked up separately and M2 generations were obtained. At the plants, which were obtained from M2 generation, chlorophyll mutants were determined and atrazine selection was made. The percentage of chlorophyll mutants for Amsoy-71, Coles and 1937 soybean varieties were found as 1.07, 1.48 and 1.32, respectively. At the end of atrazine selection, the percentages of atrazine resistant plants for Amsoy-71, Coles and 1937 soybean varieties were 0.80, 0.60 and 0.53, respectively. The percentages of atrazine tolerated plants were 1.07, 1.18 and 1.05, respectively as well. In our research; the differences among the mutants replying to atrazine in various concentrations were examined by using RAPD procedure as the molecular marker techniques in comparison with polymorphism. In the study done by using 14 primers; according to the amplification results, the differences between atrazine resistant plants were shown.

The effect of calpain-10 gene polymorphism on the development of type 2 diabetes mellitus in a Turkish population.

INTRODUCTION: The variations in the Calpain-10 gene have been suggested to be related to susceptibility to type 2 diabetes mellitus (T2DM) in different populations. In this study, we investigated the relationship between single nucleotide polymorphism (SNP)-19, -44 and -63 in the Calpain-10 gene and the development of T2DM in a Turkish population. MATERIAL AND METHODS: A total of 211 subjects were recruited: 118 patients with a diagnosis of T2DM and 93 unrelated healthy subjects. RESULTS: There were no significant differences in the genotype and allele distribution of SNPs studied between the patients with T2DM and controls (p > 0.05), whereas the frequencies of 121 haplotype and 122/121 haplotype combination were found to be higher in patients with T2DM than in controls (p < 0.05). No association was observed between the variations in the Calpain-10 gene and glycaemic control and lipid parameters (p > 0.05). The SNP-19 insertion/insertion was significantly related to increased body mass index (BMI) in male diabetic patients (p < 0.05). CONCLUSIONS: The present study indicates that 121 haplotype and 122/121 haplotype combination of SNP-19, -44 and -63 in the Calpain-10 gene are associated with the development of T2DM in Turkish patients.