Synthesis,structural chemistry and antimicrobial activity of −(−) borneol derivative

Borneol is a monoterpene that is a part of traditional Chinese and Japanese medicine. (−) borneol reacted with methanesulfonyl chloride in THF/pyridine to afford the new 1,7,7-trimethylbicyclo[2.2.1]hept-2-yl methane sulfonate derivative in excellent yield. The product is characterized by H1NMR, C¹³NMR, mass spectroscopy as well as elemental analysis and its structure was identified by X-ray single crystal diffraction. The packing of 1,7,7-trimethylbicyclo[2.2.1]hept-2-yl methanesulfonate exhibits the non-classical C-H···O hydrogen bonding in C(4) and R² ₂(8) chain and ring motifs as structural determinants. This was also confirmed by the analysis of Hirshfeld surfaces. The 1,7,7-trimethylbicyclo[2.2.1]hept-2-yl methane sulfonate antimicrobial activity was tested and compared with its parent (−) borneol against three different pathogens. Particularly, 1,7,7-trimethylbicyclo[2.2.1]hept-2-yl methane sulfonate showed high sensitivity, compared to Chloramphenicol reference material, against Escherichia coli.      

Synthesis of ω-hydroxy-α-alkyl/aryl-γ-organo-selenium and γ-organo-tellurium: a new class of organochalcogen compounds with antinociceptive activity

We present here the results on the synthesis of alkynylselenoalcohols and alkynyltelluroalcohols using the reaction of lithium-alkynylchalcogenolates, generated via the reaction of alkynyllithium with elemental Se or Te, with bromo-alcohols. The reaction proceeded cleanly under mild reaction conditions, and alkynylchalcogenoalcohols were formed in good to excellent yields. The obtained compounds 2o and 2v were screened for antinociceptive activity using the acetic acid-induced writhing reaction in mice. Compound 2o administered by oral route at 5-50 mg/kg produced a significant inhibition of the acetic acid-induced abdominal constriction in mice.     

Synthesis and evaluation of antibacterial and anti-oxidant activity of small molecular chitosan–fucoidan conjugate nanoparticles

Research on Chemical Intermediates - Low-molecular weight chitosan (LMWC) and low-molecular weight fucoidan (LMWF) have been reported to possess diverse biological activity. In this study, LMWC and...     

Antioxidant activity of β-carotene compounds in different in vitro assays

β-Carotene (BC) is the most abundant carotenoid in human diet, almost solely as(all-E)-isomer. Significant amounts of (Z)-isomers of BC are present in processed food as well as in mammalian tissues. Differences are described for the activity of various BC isomers in forming retinal and protecting against cancer and cardiovascular diseases. Eccentric cleavage of BC leads to degradation products such as carotenals. A variety of negative consequences were published for the non-vitamin A active BC metabolites, such as inducing the carcinogenesis of benzo[a]pyrene, impairing mitochondrial function, or increasing CYP activity. To increase the knowledge on the antioxidant activity, a variety of BC isomers and metabolites were tested in various in vitro assays. In the present study, no ferric reducing activity (FRAP assay) was observed for the BC isomers. Between the major BC isomers (all-E, 9Z, and 13Z) no significant differences in bleaching the ABTS●+ (αTEAC assay) or in scavenging peroxyl radicals (ROO●) generated by thermal degradation of AAPH (using a chemiluminescence assay) were detected.However, the (15Z)-isomer was less active, maybe due to its low stability. The degradation to β-apo-carotenoids increased FRAP activity and ROO● scavenging activity compared to the parent molecule. Dependence on chain length and character of the terminal function was determined in αTEAC assay with following order of increasing activity: β-apo-8'-carotenal < β-apo-8'-carotenoic acid ethyl ester < 6'-methyl-β-apo-6'-carotene-6'-one (citranaxanthin). The results indicate that BC does not lose its antioxidant activity by degradation to long chain breakdown products.     

Rapid detection and structural characterization of verapamil metabolites in rats by UPLC–MSE and UNIFI platform

High-resolution mass spectrometry (HRMS) is an important technology for studying biotransformations of drugs in biological systems. In order to process complex HRMS data, bioinformatics, including data-mining techniques for identifying drug metabolites from liquid chromatography/high-resolution mass spectrometry (LC/HRMS) or multistage mass spectrometry (MSⁿ) datasets as well as elucidating the detected metabolites’ structure by spectral interpretation software, are important tools. Data-mining technologies have widely been used in drug metabolite identification, including mass defect filters, product ion filters, neutral-loss filters, control sample comparisons and extracted ion chromatographic analysis. However, the metabolites identified by current different technologies are not the same, indicating the importance of technique integration for efficient and complete identification of metabolic products. In this study, a universal, high-throughput workflow for identifying and verifying metabolites by applying the drug metabolite identification software UNIFI is reported, to study the biotransformation of verapamil in rats. A total of 71 verapamil metabolites were found in rat plasma, urine and faeces, including two metabolites that have not been reported in the literature. Phase I metabolites of verapamil were identified as N-demethylation, O-demethylation, N-dealkylation and oxidation and dehydrogenation metabolites; phase II metabolites were mainly glucuronidation and sulfate conjugates, indicating that UNIFI software could be effective and valuable in identifying drug metabolites.     

Nano Gd2O3 catalyzed synthesis and anti-oxidant activity of new α-aminophosphonates

A one pot three-component nano Gd₂O₃ catalyzed neat reaction of 2-morpholinoethanamine and dimethylphosphite with various salicylaldehydes under microwave irradiation afforded a series of new α-aminophosphonates in high yields. The synthesized compounds were characterized by FT-IR, (¹H, ¹³C, ³¹P)-NMR, and mass spectral methods. The antioxidant activity of these compounds was evaluated against DPPH, NO, and H₂O₂ methods and found that the compound Dimethyl (2-hydroxy-5-nitrophenyl) (2-morpholinoethylamino) methylphosphonate (4h) has higher antioxidant activity than the corresponding standards.     

Influence of ethanol and ultrasound on drying,bioactive compounds,and antioxidant activity of strawberries (Fragaria × ananassa)

This study aimed to evaluate the use of ethanol (ET) and ultrasound (US) in convective drying of strawberry slices, as well as the effect on physicochemical, bioactive, and antioxidant parameters. For this, strawberry slices with a thickness of 0.005 m were pretreated with ET (in different volume fractions), US, and a combination of both. Drying kinetics were performed for control strawberry slices (without ET and US) and pretreated with 50% ethanol (ET50), 50% ethanol and ultrasonic (ET50US), 100% ethanol (ET100), and 100% ethanol and ultrasonic (ET100US) at a temperature of 60 °C. Empirical and diffusive models were fitted to the experimental data to describe the drying kinetics, and the fresh and dried slices were analyzed according to the parameters of water activity (aw), water content, total phenolic compounds (TPC), total anthocyanins (ATS), vitamin C and antioxidant activity (AA) (ABTS?+, DPPH?, and FRAP). The use of the ET100US combination provided an increase in the moisture transport process, higher drying rate, shorter process time (570 min), and reduction of a_w to a safe value (a_w <0.5), however, it sharply degraded the TPC, ATS, and AA. The ET50US pre-treatment even with a drying time of 690 min was the most efficient, since the values of TPC, ATS, and vitamin C suffered smaller reductions, where the AA varied in only 10.32%, 13.78% and 6.54% for the methods ABTS?+, DPPH?, and FRAP, respectively when compared to fresh strawberry. In this sense, it can be stated that the pre-treatment with 50% ethanol and ultrasound (ET50US) showed less reduction in the degradation of bioactive and antioxidant properties, and in the minimization of drying time for strawberry slices.     

Therapeutic effects of soy isoflavones on α-amylase activity, insulin deficiency, liver-kidney function and metabolic disorders in diabetic rats

Natural estrogens have demonstrated a wide variety of biological activities, which makes them a good candidate for the treatment of diabetes. In vitro, this study evidenced that isoflavones enhanced insulin secretion and inhibited α-amylase activity. In vivo, the findings indicated that soy isoflavones stimulated insulin secretion, increased the hepatic glycogen content and suppressed blood glucose level. The soy isoflavones were also protected hepatic-kidney functions showed by the significant increase in superoxide dismutase, catalase and glutathione peroxidase activities and the decrease in thiobarbituric acid reactive substances, total bilirubin, creatinine and transaminases content. Moreover, soy isoflavones induced a decrease in LDL-cholesterol and triglycerides and an increase in HDL-cholesterol in plasma and liver. Overall, the findings of the current study indicate that soy isoflavones exhibit attractive properties and can, therefore, be considered a promising candidate for future application as alternative therapeutic agents, particularly in the development of anti-diabetic and hypolipidaemic drugs.     

Developments in the synthesis of α,α-dibromoacetophenones and related compounds

Increasing demand of α,α-dibromoketones, as highly reactive and easy-to-handle precursors to carry out selective organic transformations, to synthesize heterocyclic compounds of therapeutic interest and lack of any compilation on this subject prompted us to assemble the methods available for their synthesis.     

Synthesis,characterization of inclusion compounds of amygdalin with β-cyclodextrin and sod-like activity and cytotoxicity on hela tumor cells

In this work is presented the synthesis of the inclusion complexes of amygdalin with β-cyclodextrin by three methods: kneading, co-precipitation and freeze drying and their characterization.The inclusion compounds were synthesized using a molar ratio of amygdalin: β-cyclodextrin of 1:1. Synthesized compounds were analyzed by FTIR spectroscopy, X-rays, thermal analysis and the results confirm the formation of inclusion compounds by amygdalin with β-cyclodextrin.The studies carried out have shown the protective effect of amygdalin-β-cyclodextrin compounds obtained by freeze drying, kneading and coprecipitation against free radicals (SOD-like activity in vivo) and the results of in vitro cell cytotoxicity of the compounds on HeLa cell line compared to pure amygdalin. Compound obtained by freeze drying has the best SOD-like activity and cytotoxicity on HeLa tumor cells, so it may be considered as potential therapeutic agent.     

Aryloxy and benzyloxy compounds of zirconium: Synthesis, structural characterization and studies on solvent-free ring-opening polymerization of ?-caprolactone and δ-valerolactone

A series of aryloxy compounds and benzyloxy derivatives of Zr(IV) were synthesized in good yields and purity, employing the alcoholysis route. They were completely characterized with different spectroscopic techniques and single crystal X-ray diffraction. A high degree of fluxional behavior of these compounds was understood through variable-temperature NMR studies. X-ray diffraction studies prove that these compounds exist as dimers in the solid state. They are potent catalysts for the ring-opening polymerization of ?-caprolactone (CL) and δ-valerolactone (VL) resulting in high polymers with good number average molecular weights (M_n) and molecular weight distributions (MWDs). The degree of control in these polymerizations was found to be superior with the zirconium compounds when compared with the titanium analogues. The rate of polymerization was found to be slower for the zirconium compounds, as realized from kinetic studies. Analysis of the MALDI-TOF and ¹H NMR spectra of low molecular weight oligomers of CL synthesized using these compounds reflect that these polymerizations proceed by the activated monomer mechanism.     

Synthesis and antimicrobial activity of novel quinazolinone–thiazolidine–quinoline compounds

A series of 2-(2-chloroquinolin-3-yl)-5-((aryl)benzylidene)-3-(4-oxo-2-phenylquinazolin-3(4H)-yl)thiazolidin-4-ones (V)_1–12 have been synthesized. In order to establish optimization of different parameters of chemical transformation, that is the reaction pathway for each step and reaction conditions in the each step, in the present paper, different solvents and catalysts were used. The structures of the synthesized compounds were assigned on the basis of elemental analysis, IR, ¹H NMR and ¹³C NMR spectral data. All the newly synthesized compounds were screened against various strains of bacteria and fungi.     

Synthesis,antifungal activity and 3D-QSAR study of novel nopol-based 1,3,4-thiadiazole–thioether compounds

Research on Chemical Intermediates - A series of novel nopol derivatives containing 1,3,4-thiadiazole–thioether moiety were synthesized from β-pinene, which is a natural, abundant and...     

Syntheses and structures of metal–metal triply bonded M2R6 compounds: consideration of starting materials,stability, and structural parameters

The syntheses and structures of four homoleptic metal–metal triply-bonded M₂R₆ compounds [Mo₂(CH₂CMe₂Ph)₆, 1; Mo₂(CH₂SiMe₂Ph)₆, 2; W₂(CH₂SiMe₂Ph)₆, 3; and W₂(CH₂Ph)₆, 4] are reported. The synthetic effort suggests that ditungsten compounds are inherently more difficult to prepare and more thermally sensitive than dimolybdenum compounds, probably as a result of the larger dimetal core the ligands must protect. The structural data confirm that dimetal hexaalkyls exhibit shorter M≡M distances than do dimetal hexaalkoxides, even in a matched pair case where steric differences are minimal.     

Synthesis and characterization of substituted salicylate zirconium compounds and their catalytic activity over ε-caprolactone

In this study, zirconium salicylate compounds (1–6) were prepared by reaction of zirconium(IV) propoxide with 5-chlorosalicylic acid, 4-hydroxysalicylic acid, and 5-nitrosalicylic acid in 1-propanol, respectively. All these compounds (1–6) were characterized by ¹H, ¹³C NMR, FTIR, mass spectroscopy, elemental, and thermogravimetric analyses. These compounds were tested as catalysts in polymerization of ε-caprolactone and were effective. Polycaprolactone was characterized by ¹H, ¹³C NMR, and gel permeation chromatography. The number of salicylate ligands (bonded to zirconium atom) effects and substituents (on salicylate ligands) effects on the polymerization reactions were investigated first time by this study.     

First-principles calculations to investigate structural,electronic, optical,and transport properties of half-Heusler VFeZ (Z = N and P) compounds

This research work investigates the structural, electronic, optical, and thermoelectric characteristics of VFeZ (Z = N and P) half-Heusler compounds. The study employs the full-potential linearized augmented plane wave (FP-LAPW) method integrated into the WIEN2K algorithm, serving as the underpinning framework for density functional theory (DFT) analysis. In the study, we use the PBE generalized gradient approximation (PBE-GGA) to identify numerous parameters associated with structural and elastic properties. Lattice parameter results are in agreement with previous outcomes. Moreover, computed elastic parameters satisfy the criterion for stability. In the cubic structure VFeZ (Z = N and P) is ductile, to enhance the computations of electronic characteristics, Tran and Blaha's modified Becke-Johnson potential (TB-mBJ) is used. Our simulations demonstrate that the materials exhibit semiconductor behavior, with a direct band gap for VFeZ (Z = N and P). Strong UV absorption is found via optical experiments suggest compounds are suitable for optical application. Furthermore, study of the thermoelectric properties suggests its application in the thermoelectric generators.     

Experimental and theoretical studies of Palladium-hydrazide complexes’ interaction with DNA and BSA,in vitro cytotoxicity activity and plasmid cleavage ability

New palladium complexes with general formula trans-[Pd(L)₂(OAc)₂] (1,2), (L = Benzhydrazide and 2-Furoic hydrazide) have been synthesized and characterized with various methods including elemental analysis, FT-IR, ¹HNMR and mass spectroscopy. Afterward their interactions with bovine serum albumin and calf thymus deoxyribonucleic acid have been investigated by UV–vis absorption, fluorescence emission and circular dichroism spectroscopy. Also, site‐selective replacement experiments with site probes have been carried out. Analysis of fluorescence spectrum indicated static quenching mechanism. Spectroscopic measurements for DNA binding showed the groove binding to DNA for both complexes. Furthermore, cytotoxicity studies of complexes and cis-platin have been done against colon carcinoma (CT26) and breast cancer (4T1) cell lines. Evaluation of complexes (1) and (2) on induction of apoptosis in CT26 cells has been done. Finally, plasmid cleavage ability of (1) and (2) was investigated by gel electrophoresis that indicate the more activity of (1) than (2).     

Extraction and determination of biologically active components of St. John’s wort and its pharmaceutical preparations

A procedure is developed for the determination of biologically active substances (BAS) of common St. John’s wort (Hypericum perforatum L.) by HPLC using two columns, Luna C18, 100 Å (for the determination of phenolcarboxylic acids and flavonoids), and Onyx Monolithic C18 (for the determination of phloroglucinols and naphthodianthrones), in the gradient elution mode with diode array detection. The detection limits for analytes are 0.05–0.20 μg/mL. To optimize the conditions, we studied the extraction of biologically active substances from St. John’s wort by a water–ethanol solution at different temperatures and pressures and under the effect of microwave radiation and ultrasound. The maximum amounts of substances were extracted in a dynamic mode under heat and pressure. The procedure was applied to the St. John’s wort samples of different brands and some pharmaceutical products based on it. The components of extracts were identified by retention times, UV spectra, and mass spectra. It was shown that the content of biologically active substances in pharmaceutical samples of St. John’s wort depends on the herb habitat. It was shown that hyperforin decomposed in pharmaceutical formulations based on St. John’s wort during storage.     

An assay for determination of rat adrenal catechol-O-methyltransferase activity: comparison of spontaneously hypertensive rats and Wistar–Kyoto rats

A method has been developed for measurement of catechol-O-methyltransferase (COMT) activity in the rat adrenal gland. Epinephrine, synthesized in the adrenal gland, was used as substrate, and its enzymatic product, metanephrine, was quantified by high-performance liquid chromatography (HPLC) with fluorescence detection. The method has sufficient precision and accuracy. Soluble (S) and membrane-bound (MB) COMT activity in Wistar–Kyoto (WKY) rats was 20.7±3.5 and 18.6±3.4 pmol min^–1 mg^–1 protein (n=5), respectively. To clarify the role of adrenal COMT in blood-pressure regulation, S and MB COMT activity in spontaneously hypertensive rats were determined. Respective activity was 18.6±3.4 and 17.0±1.1 pmol min^–1 mg^–1 (n=5), which is similar to that in WKY rats. This finding suggests that COMT in the adrenal gland might not be related to blood pressure regulation.