Generation of radical species from dihydropyrazines having DNA strand-breakage activity and other characteristics

The various biological activity of dihydropyrazines(DHPs)due to the radical generation potency has been described in previous papers. Detailed data about radical species generating be mentioned here. The electron spin resonance (ESR) spin-trapping technique revealed that DHPs generate free radical species such as ·OH, ·OOH, ·CHR(2) and ·CR(3). Oxygen radicals and two carbon-centered radicals were detected as adducts of the spin traps DMPO and DBNBS, respectively. All the 5,5-dimethyl-1-pyrroline-N-oxide (DMPO)- and 3,5-dibromo-4-nitrosobenzenesulfonate (DBNBS)-adducts of compounds DHP-1-8 exhibited approximately the same signal patterns, with various levels of intensity depending on the substituent of the dihydropyrazine ring. The ESR signal intensity of DHPs also increased remarkably upon addition of Cu(2+), resulting that the effects of DHPs were enhanced.     

The relationship between the chemical structures of dihydropyrazine derivatives and DNA strand-breakage activity

Dihydropyrazine, a compound derived from sugars, possesses DNA strand-breakage activity. The relationship between the activity as assayed using pBR 322 ccc-DNA and the chemical structures of derivatives of dihydropyrazine (DHPs) has been investigated. The addition of Cu(2+) enhanced the activity remarkably. The introduction of a methyl or phenyl group onto the DHP ring or a cyclohexyl group fused onto the DHP ring also increased the activity. These properties indicated that the activity was due to the facility of electron release from the DHP ring, followed by radical generation. The determination of ionization potential and electrostatic potential values, and bond dissociation energy via semi-empirical MO calculations suggested strongly that the activity is induced by a DHP ring structure that contains a configuration suitable for hyperconjugation.     

Synthesis of new carbohydrate-containing cationic alkyl glycerolipids with antitumor activity

Russian Chemical Bulletin - New non-phosphorous carbohydrate-containing cationic alkyl glycerolipids bearing a ter- minal glycosyl moiety were synthesized. An approach used for the preparation of...     

Synthesis of a new nitrogenated drimane derivative with antifungal activity

Drimane sesquiterpenes are highly valuable due to their strong biological activity. In this work, we report the enhanced antifungal activity of 11-guanidinodrimene, a new compound derived from drimenol. The binding of the guanidine group at the C-11 carbon increased the antifungal activity when tested against Candida albicans, one of the most commonly found human pathogens.     

Synthesis,characterization, DNA binding,antibacterial, and antioxidant activity of new bis-phthalimides

New bis-phthalimides were synthesized by 2: 1 condensation of phthalic anhydride and tetrachlorophthalic anhydride with 1,2,4-triazole-3,5-diamine, pyridine-2,6-diamine, and 4-hydroxypyrimidine- 2,6-diamine. The synthesized compounds were characterized by elemental analyses and IR, ¹H NMR, and mass spectra. Their interaction with calf thymus DNA (ct-DNA) was studied by UV-Vis spectrophotometry, cyclic voltammetry, and viscosity measurements, which revealed intercalative mode of binding to ct-DNA. Antibacterial activity of the synthesized compounds against Escherichia coli and Streptococcus mutans was assessed in vitro by the agar well diffusion method. The antioxidant activity of these compounds was estimated by DPPH assay.     

Synthesis,characterization, DNA interaction and cleavage activity of new mixed ligand copper(II) complexes with heterocyclic bases

Mixed ligand complexes having the formulae Cu(RPO)₂Py₂, Cu(RPO)₂Im₂ and Cu(DBO)₂Py₂ [RPO = resacetophenone oxime, DBO = 2,4-dihydroxybenzophenone oxime, Py = pyridine and Im = imidazole] have been synthesized and characterized by UV–Vis, IR, ESR, cyclic voltammetry and magnetic susceptibility methods. Absorption studies revealed that each of these octahedral complexes is an avid binder of calf thymus DNA. The apparent binding constants for mixed ligand complexes are in order of 10⁴–10⁵ M⁻¹. Based on the data obtained in the DNA binding studies a partial intercalative mode of binding is suggested for these complexes. The nucleolytic cleavage activity of the adducts was carried out on double stranded pBR322 circular plasmid DNA by using a gel electrophoresis experiment in the presence and absence of oxidant (H₂O₂). All the metal complexes cleaved supercoiled DNA by hydrolytic and oxidative paths. The oxidative path dominates the hydrolytic cleavage. The hydrolytic cleavage of DNA is evidenced from the control experiments showing discernable cleavage inhibition in the presence of the hydroxyl radical inhibitor DMSO or the singlet oxygen quencher azide ion.     

Synthesis,interaction with double-helical DNA and biological activity of new Pt(II) and Pd(II) complexes with phenylglycine

The mononuclear palladium(II) (1) and platinum(II) (2) complexes containing phenylglycine have been synthesized and characterized by elemental analysis, IR spectra, and ¹H NMR spectra. The structure of 1 was determined by X-ray diffractometry. The interaction between the complexes and fish sperm DNA (FS-DNA), adenosine-5′-triphosphate (ATP), and adenine (Ade) were investigated by UV absorption spectra, the interaction mode of the complex binding to DNA was studied by fluorescence spectra and viscometry. The results indicate that the two complexes have different binding affinities to DNA, complex 2 > complex 1. Gel electrophoresis assay demonstrates that the two complexes have the ability to cleave pBR322 plasmid DNA. Cytotoxicity experiments were carried out toward four different cancer cell lines, and 1 shows lower inhibitory efficiency than 2, consistent with the binding affinities towards DNA.     

Synthesis of new N-analogous corollosporine derivatives with antibacterial activity by laccase-catalyzed amination

Corollosporine isolated from the marine fungus Corollospora maritima and N-analogous corollosporines are antimicrobial substances. Owing to the basic structure of the N-analogous corollosporines, they have become an attractive target for laccase-catalyzed derivatisation. In this regard we report on the straightforward laccase-catalyzed amination of dihydroxylated arenes with N-analogous corollosporines. In biological assays the obtained amination products are more active than the parent compounds.     

Synthesis of new heterocycles festooned with thiophene and evaluating their antioxidant activity

The chemical performance of 5-bromo-2-(bromoacetyl)-thiophene ( 1 ) was tested toward the reaction with numerous bi-nucleophilic reagents (namely; 2-aminobenzothiazoles, 2-aminothiazole, 2-aminotetrazole, 2-aminotriazole, 2-aminopyridines, 2-aminobenzimidazole and o-phenylenediamine). Therefore, a series of bridged nitrogen heterocycles bearing thiophene moiety 3 , 5 , 7 , 9 , 11 , 13 and 15 , respectively was synthesized. In addition, the reaction of 5-bromo-2-(bromoacetyl)-thiophene with the thiocarbamoyl compounds 17 , 19 and/or 24 afforded the corresponding thienyl-thiazoles 18 or dithien-2-yl ketones 20 and 25 , based on the reaction conditions. Treatment of 1 with 2-mercapto-4,6-dimethylnicotinonitrile was achieved to obtain the target dithien-2-yl ketone 28 . The new synthesized scaffolds were examined for their antioxidant activity by means of ABTS antioxidant assay. The thienyl-thiazole scaffold 18c and 2-((2-[thiophen-2-yl]-2-oxoethyl)thio)nicotinonitrile derivative 27 displayed a reasonable radical scavenging activity.     

Synthesis and biological activity of new derivatives with the preserved carane system

Abstract

Terpenoid derivatives, which contain a preserved carane system in their structure, exhibit a broad spectrum of biological activities. Among them, we can distinguish insecticides, structures with pharmacological application etc. In the presented paper, the substrate - (–)-cis-caran-trans-4-ol was transformed using the reactions of typical organic synthesis to obtain novel derivatives. Most importantly, bromolactone ((–)-(1R,4R,6S)-2'-(bromomethyl)-4,7,7-trimethylspiro[bicyclo[4.1.0]heptan-3,3'-furan]-5'(4'H)-one) with the preserved carane system was synthesized. This bromolactone was tested for antifeedant activity against the lesser mealworm, Alphitobius diaperinus Panzer, and peach potato aphid (Myzus persicae). In addition, its moderate antibacterial activity was observed against the Bacillus subtilis strain (with Minimal Inhibitory Concentration of 200 µg/mL).     

Synthesis and antihypoxic activity of new aminothiadiazolylbenzodioxane derivatives

Russian Journal of Organic Chemistry - Intramolecular cyclization of 2-(2,3-dihydro-1,4-benzodioxine-2-carbonyl)hydrazine-1-carbothioamide by the action of concentrated sulfuric acid gave...     

Synthesis and antiviral activity of new indole-based heterocycles

New 1,2,4-triazolo[3,4-b]-1,3,4-thiadiazine and 1,3-thiazole derivatives incorporating indole nucleus were prepared using 3-acetylindole as precursor and evaluated for their antiviral activity against herpes simplex type 1 (HSV-1).     

Synthesis and tuberculostatic activity of new benzimidazole derivatives

The reactions of o-phenylenediamine and 3,4-diaminotoluene with such acids as 3-cyclohexylpropionic, 4-phenylbutyric, 4-cyclohexylbutyric, 3,3-diphenylpropionic, and 3,4-dimethoxyphenylacetic resulted in the formation of the corresponding 2-substituted benzimidazoles. These compounds were transformed into methane-and benzenesulfonamide derivatives. The benzimidazole derivatives obtained were tested in vitro for their tuberculostatic activity. Compounds with good activity (MIC 6.2-25 μg/ml) have been found. Published from Khimiya Geterotsiklicheskikh Soedinenii, No. 5, pp. 697–700, May, 2006.     

Synthesis and cytotoxic activity of new indolylpyrrole derivatives

The current approach described the synthesis of a new series of indolylpyrrole derivatives through multicomponent reaction of α-cyano chalcones, appropriate aldehydes, and ammonium acetate in refluxed acetic acid. The chemical structures of the designed compounds were confirmed with spectroscopic data and elemental analysis and then tested for their in vitro cytotoxic activity by SRB assay method towards three cell lines involving human Prostate adenocarcinoma; metastatic cells (PC-3), human ovary adenocarcinoma (SKOV3) and human dukes' type B, colorectal adenocarcinoma (LS 174 T). Most significant activity provided with compounds 5c, 5h and, 5j against prostate cancer cells (PC-3) with IC50s of 3.30 ± 0.20, 3.60 ± 0.10, and 3.60 ± 0.90 µg/ml, respectively. In human ovarian carcinoma (SKOV3), the compounds 5a, and 5i have stronger cytotoxicity with IC50s of 1.20 ± 0.04, 1.90 ± 0.50 µg/ml, respectively than the standard doxorubicin (IC50 = 2.20 ± 0.02 µg/ml). On the other hand, only compound 5a has the ability to diminish the viability of LS174T cells in an active manner with IC50 2.80 ± 0.10 µg/ml. Consequently, this effort offers groundwork for additional examination of nominated indolylpyrroles as antiproliferative agents.     

Synthesis,reactions with DNA,and antitumor activity of platinum complexes with aminonitroxyl radicals

The work is a review of the data on the synthesis of mono- and biradical Pt^II complexes with mono- and diaminonitroxyl radicals, as well as of a binuclear complex with diaminonitroxyl radical. A “mild” method is considered for the synthesis of a number of Pt^IV nitroxyl complexes (9–11), whose lipophilicity varies within a wide range due to the trans-ligands, i.e., the linear aliphatic acid moieties. Correlations between the structures of the complexes, efficiency of their binding to DNA, and the effect of this binding on the DNA stability were established. Cytotoxic properties of the complexes against the HeLa, H1299, and MCF7 tumor cells, the effect of the complexes on the cell cycle, and the p53 protein expression were studied. The data on the antitumor activity of the complexes in the animal tumor model, P388 leukemia, are given. The rate of the development of resistance to complex 10a for P388 leukemia is 2.5 times lower than the corresponding value for cisplatin. It was found that a synergistic enhancement of antitumor activity is observed when low doses of cisplatin and complexes 9b or 10b are simultaneously administered. The specificities of biological activity of the platinum nitroxyl complexes are presumably due to the antioxidant properties of the nitroxyl pharmacophore and the ability of these complexes to cause the p53-independent tumor cell death.     

New Highlights in the Synthesis of 4‐Aryl‐1,4‐dihydropyrazines

The 4‐aryl‐1,4‐dihydropyrazines were prepared via the cyclization of N,N‐bisalkylated anilines with ammonium acetate. These reactions were aided by improvements in the synthesis of N,N‐bisalkylated anilines which were alkylated with anilines using ethyl 2‐diazo acetoacetate in a reaction catalyzed by rhodium acetate in the absence of oxygen. A possible mechanistic route is postulated on the basis of the isolation of the N‐alkylation intermediates, which were determined to be N‐aryloxamates by ¹H NMR data and X‐ray diffraction.     

Synthesis of new fluorinated Tebufenpyrad analogs with acaricidal activity through regioselective pyrazole formation

In previous studies, our group has shown that the use of fluorinated alcohols such as trifluoroethanol (TFE) and hexafluoroisopropanol (HFIP) as solvents dramatically increases the regioselectivity in the pyrazole formation from 1,3-diketone with methylhydrazine. We have now applied this synthetic method to the preparation of new fluorinated pyrazoles, which have then been used as synthetic intermediates in the preparation of fluorinated analogs of Tebufenpyrad, a commercial acaricide. These compounds display a strong acaricidal activity that is either comparable to or better than that of the commercial compound.     

Synthesis of new pyrimidine nucleoside derivatives with nitric oxide donors for antiviral activity

New pyrimidine nucleoside derivatives with nitric oxide(NO) donor were systematically synthesized.The antivirus activities of these nucleoside analogues against vesicular stomatitis virus(VSV) in Wish cell were evaluated.It was demonstrated that most of compounds had stronger antiviral acitivity than acyclovir,while their toxicities were similar or lower to acyclovir.