Synthesis and preclinical pharmacological evaluation of a novel 99mTc–shikonin as a potential tumor imaging agent

Shikonin was isolated from Ratanjot pigment then the obtained shikonin was well characterized. This study is aimed to optimize radiolabeling yield of shikonin with ^99mTc with respect to factors that affect the reaction conditions such as shikonin amount, SnCl₂·2H₂O amount, reaction time and pH of the reaction mixture. In vitro stability of the radiolabeled complex was checked and it was found to be stable for up to 6?h. Biodistribution studies showed that, ^99mTc?Cshikonin accumulate in tumor sites with higher T/NT than other currently available ^99mTc(CO)₃-VIP, ^99mTc?Cnitroimidazole analogues and ^99mTc?Cpolyamine analogues indicating that shikonin deliver ^99mTc to the tumor sites with a percentage sufficient for imaging and can overcome many drawbacks of other radiopharmaceuticals used for tumor imaging.     

Synthesis and properties of a functionalized heterobimetallic Re(I)–Gd(III) complex as a potential dual-contrast agent for molecular imaging

In the design of dual-imaging probes, the first functionalized and neutral heterobimetallic Re(I)–Gd(III) complex, highly soluble in aqueous solutions, has been prepared. This system exhibits interesting photophysical properties (λ_em = 578 nm, ? = 1.4%) for optical imaging and substantial higher relaxivity (r₁ = 6.6 mM⁻¹ s⁻¹ at 0.47 T and 37 °C) than the clinically used MRI contrast agents. Moreover, this system incorporates an aromatic ester functionality suitable for bioconjugation.     

Synthesis of techentium-99m labeled clinafloxacin (99mTc�CCNN) complex and biological evaluation as a potential Staphylococcus aureus infection imaging agent

In the present study synthesis of the ^99mTc?CCNN complex and its efficacy as a prospective Staphylococcus aureus (S. aureus) infection imaging agent was assessed. The ^99mTc?CCNN complex was characterized in terms of stability in saline, serum, in vitro binding with S. aureus and in vivo percent absorption in male Wister rats (MWR) infected with live and heat killed S. aureus. Radiochemically the ^99mTc?CCNN complex showed stable behavior in saline and serum at different intervals. At 30 min after reconstitution the complex showed maximum radiochemical purity (RCP) yield of 97.55 ± 0.22%. The RCP yield decreased to 90.50 ± 0.18% within 240 min. In serum, 18.15% unwanted side product was appeared within 16 h of the incubation. In vitro saturated binding with S. aureus was observed at different intervals with a 62.00% maximum at 90 min. Normal percent in vivo uptake was observed in MWR artificially infected with live S. aureus with a five times higher in the infected muscle as compared to the inflamed and normal muscles. No difference in the percent uptake of the complex in MWR infected with heat killed S. aureus in the infected, inflamed and normal muscles were observed. Based on the promising in vitro and in vivo radiochemical and biological characteristics, we recommend the ^99mTc?CCNN complex for in vivo localization of the S. aureus infectious foci.     

Dispersive liquid–liquid microextraction using a surfactant as disperser agent

A novel and efficient surfactant-assisted dispersive liquid–liquid microextraction combined with high-performance liquid chromatography–photodiode array detection was developed for the determination of phenylurea herbicides in water samples. Based on this procedure, which is a dispersive-solvent-free technique, the extractant is dispersed in the aqueous sample using methyltrialkylammonium chloride. Compared with the conventional dispersive liquid–liquid microextraction, the new extraction method has many advantages such as higher extraction efficiency, low cost, reduced environmental hazards, and consumption of less extracting solvent. A few microliters of chloroform containing an appropriate amount of methyltrialkylammonium chloride (mixture of C8–C10) was used to extract the analytes from water samples. The main parameters relevant to the extraction process (namely, type of surfactant, selection of extractant solvent, extractant volume, surfactant concentration, ionic strength, and extraction time) were investigated. The performed analytical procedure showed limits of detection ranging from 2.3 to 18 ng/L, and precision ranges from 0.6% to 2.0% (as intra-day relative standard deviation, RSD) and from 1.3% to 8.3% (as inter-day RSD) depending on the analyte. The method showed good linearity between 0.04 and 40 μg/L with squared correlation coefficients better than 0.9920. This newly established approach was successfully applied to spiked real water samples.     

Sulfonimidamide as a directing agent for Pd-catalyzed regioselective oxidative C–H acyloxylation of arenes

In this report, we describe the utilization of sulfonimidamide (SIA) as a novel directing group for a Pd-catalyzed regioselective oxidative C–H acyloxylation of aryl group of N-aroyl part of SIA in moderate to good yields in the presence of (Diacetoxyiodo)benzene (PhI(OAc)₂) as an oxidizing agent and alkanoic acid as solvent. The solvent alkanoic acid is found to be the source of acyloxylation.     

Development of a dispersive liquid–liquid microextraction method for determination of palladium in water samples using dicyclohexano-18- crown-6 as extracting agent

A new separation procedure for determination of palladium using dispersive liquid–liquid microextraction with dicyclohexano-18-crown-6 as complexing reagent was developed. In this method, potassium–dicyclohexano-18-crown-6 was used as a hydrophobic complex for the microextraction of palladium as PdCl₄ ^2? complex ion. The main factors affecting DLLME efficiency, such as type and volume of extractant and disperser solvent, concentration of chelating reagent, concentration of KCl and pH were optimized. Under the optimal conditions, the limit of detection for palladium was 16.0 ng mL^?1 with enrichment factor of 138. The present method was applied to the determination of palladium in water samples with satisfactory analytical results. The method was simple, rapid, cost efficient and sensitive for the extraction and preconcentration of palladium.     

Radical scavenging properties of a flavouring agent–Vanillin

Using pulse radiolysis technique, the one-electron oxidation of vanillin (V-OH) with azide radicals, at pH 6 and 9 resulted in the formation of vanillin phenoxyl radical with k = 6.7 × 10⁷ and 2.5 × 10⁹ dm³ mol^-1 s^-1, respectively. The transient absorption spectra of the vanillin phenoxyl radical (V-O) formed either at pH 6 or 9, showed a _max at 410 nm. At pH 5, the OH radicals seem to form an adduct with vanillin, _max at 430 nm and k(OH + V-OH) = 3.3 × 10⁹ dm³ mol^-1 s^-1, while at pH 9, the OH radical reaction resulted in the formation of vanillin phenoxyl radical with _max at 410 nm and k(OH + V-O-) = 6.6 × 10⁹ dm³ mol^-1 s^-1. The reactivity of NO₂radicals with vanillin is lower by orders of magnitude signifying an incomplete reaction. In general, the rate constants for the reaction of OH, N, NO radicals with vanillin were higher at pH 9 than at the lower pH. Its reactivity with other one-electron oxidants like CCl₃OO, CHCl₂OO and CH radicals and the ability to chemically repair tryptophanyl and guanosyl radicals with k = 1.5 - 4 × 10⁷ dm³ mol^-1 s^-1 indicate its antioxidative behaviour.     

Synthesis and biological distribution of 99mTc–norfloxacin complex, a novel agent for detecting sites of infection

The optimization of the radiolabeling yield of ciprofloxacin analogous, norfloxacin, with technetium-99m (^99mTc) was described. Dependence of the labeling yield of ^99mTc–norfloxacin complex on the concentration of norfloxacin, SnCl₂·2H₂O content, pH of the reaction mixture and reaction time was studied. Norfloxacin was labeled with ^99mTc at pH 3 with a labeling yield of 95.4% by using 5 mg norfloxacin, 50 μg SnCl₂·2H₂O and 30 min reaction time. The formed ^99mTc–norfloxacin complex was stable for a time up to 3 h. Biological distribution of ^99mTc–norfloxacin complex was investigated in experimentally induced inflammation rats using Staphylococcus aureus (bacterial infection model) and heat killed Staphylococcus aureus and turpentine oil (sterile inflammation model). In case of bacterial infection, the T/NT value for ^99mTc–norfloxacin complex was found to be 6.9 ± 0.4 which was higher than that of the commercially available ^99mTc–ciprofloxacin under the same experimental condition.     

Multicomponent Peptide Stapling as a Diversity-Driven Tool for the Development of Inhibitors of Protein–Protein Interactions

Stapled peptides are chemical entities in-between biologics and small molecules, which have proven to be the solution to high affinity protein–protein interaction antagonism, while keeping control over pharmacological performance such as stability and membrane penetration. We demonstrate that the multicomponent reaction-based stapling is an effective strategy for the development of α-helical peptides with highly potent dual antagonistic action of MDM2 and MDMX binding p53. Such a potent inhibitory activity of p53-MDM2/X interactions was assessed by fluorescence polarization, microscale thermophoresis, and 2D NMR, while several cocrystal structures with MDM2 were obtained. This MCR stapling protocol proved efficient and versatile in terms of diversity generation at the staple, as evidenced by the incorporation of both exo- and endo-cyclic hydrophobic moieties at the side chain cross-linkers. The interaction of the Ugi-staple fragments with the target protein was demonstrated by crystallography.     

Sol–gel synthesis of silica containers using a corrosion inhibitor,catamine AB,as a templating agent

It has been shown that silica container particles containing a large amount (~1 g/g of SiO₂) of a corrosion inhibitor, catamine AB, can be obtained, with the inhibitor being loaded at the stage of the sol–gel synthesis of the particles by using catamine micelles as a template. Being introduced into an H₂S-containing aggressive aqueous medium, such containers protect rather efficiently carbon steel from hydrogen-sulfide corrosion and hydrogenation. The protection effect seems to be realized via not only the release (desorption) of catamine AB molecules from the containers, but also the adsorption of the products of gradual dissolution of silica matrix on the surface of metal being protected.     

Utilization of bromination reactions for the determination of carbamazepine using bromate–bromide mixture as a green brominating agent

One titrimetric and two spectrophotometric procedures have been developed for the assay of carbamazepine (CBZ) in bulk drug, formulations and spiked human urine. The methods are based on the bromination of CBZ by the bromine generated in situ by the action of the acid on the bromate–bromide mixture. The twin advantages of avoiding liquid bromine and analysis in a cost-effective manner are realized. In titrimetry, the drug was treated with a known excess of bromate–bromide mixture in hydrochloric acid medium followed by the determination of unreacted bromine iodometrically. Spectrophotometry involves the addition of a measured excess of bromate–bromide reagent in acid medium to CBZ, and after the reaction is ensured to be complete, the residual bromine was determined by reacting with a fixed amount of either methyl orange and measuring the absorbance at 510 nm (method A) or indigo carmine and measuring the absorbance at 610 nm (method B). Titrimetric procedure is applicable over the range of 1.00–7.50 mg CBZ, and the calculations are based on a 1:1 reaction stoichiometry (CBZ:KBrO₃). In spectrophotometric methods, Beer’s law is valid within concentration ranges of 0.25–1.50 and 0.50–6.00 μg ml⁻¹ CBZ for methods A and B, respectively. The proposed methods were successfully applied to the determination of CBZ in tablets and syrup, in addition to spiked human urine by the spectrophotometric methods, with mean recoveries of 95.50–104.0% and the results were statistically compared with those of an official method by applying Student’s t-test and F-test.     

Novel ~(99m)Tc labeled σ receptor ligand as a potential tumor imaging agent

Sigma (σ) receptors are a distinct class of proteinsexisting in at least two subtypes termed σ1 and σ2[1].They are expressed in the central nervous system, en-docrine, immune and certain peripheral tissues andmay play an important role in regulating an…     

Formulation and preclinical evaluation of 99mTc–gemcitabine as a novel radiopharmaceutical for solid tumor imaging

The aim of this study is the formulation of a new radiopharmaceutical for imaging solid tumor bearing. Gemcitabine is a nucleoside analogue used as chemotherapeutic agent. Gemcitabine was formulated and radiolabeled with one of the most important diagnostic radioactive isotopes (technetium-99m) to be investigated in solid tumor imaging. The labeling parameters such as gemcitabine amount, stannous chloride amount, pH of the reaction mixture, and reaction time were optimized. ^99mTc–gemcitabine was prepared at pH 9 with a maximum labeling yield of 96 ± 0.3 % without any notable decomposition at room temperature over a period of 8 h. The preclinical evaluation and biodistribution in solid tumor bearing mice showed that ^99mTc–gemcitabine had solid tumor selectivity, preclinical high biological accumulation in tumor cells and high retention. Tumor/normal muscle (T/NT) ratios increased with time showing high T/NT ratio (T/NT = 4.9 ± 0.27 at 120 min post injection) and high Tumor/Blood ratio (3.4 ± 0.06), suggesting ^99mTc–gemcitabine as a novel solid tumor imaging agent.     

99mTc–meropenem as a potential SPECT imaging probe for tumor hypoxia

Meropenem was successfully radiolabeled with ^99mTc in high labeling yield (92 ± 2%) and stability (~6 h). ^99mTc–meropenem showed high accumulation in tumor hypoxic tissue (4.193% injected dose/g organ). ^99mTc–meropenem showed high ability to differentiate the tumor tissue from inflamed or infected tissues in different mice models as its T/NT ratio ~4 in case of tumor mice model while T/NT ratio ~1 in case of inflamed mice model. So, ^99mTc–meropenem showed high selectivity in comparison with FDG-PET and ^99mTc-nitroimidazole analogues. Thus, ^99mTc–meropenem could be used as a selective potential imaging agent for diagnosis of tumor hypoxia.     

Radiosynthesis and biodistribution studies of [62Zn/62Cu]–plerixafor complex as a novel in vivo PET generator for chemokine receptor imaging

In order to develop a possible C-X-C chemokine receptor type 4 (CXCR4) imaging agent for oncological scintigraphy, [⁶²Zn]labeled 1,1′-[1,4-phenylenebis(methylene)]bis-1,4,8,11-tetraazacyclotetradecane ([⁶²Zn]-AMD3100) was prepared using in-house made [⁶²Zn]ZnCl₂ and AMD-3100 for 1 h at 50 °C (radiochemical purity: >97 % ITLC, >96 % HPLC, specific activity: 20–22 GBq/mmol) in acetate buffer. The complex showed highly hydrophilic properties (log P = ?1.114). Stability of the complex was checked in presence of human serum (37 °C) and in final formulation for 1 day. The biodistribution of the labeled compound in vital organs of wild-type Sprague–Dawdley rats were determined and compared with that of free Zn²⁺ cation up to 6 h. Co-incidence imaging of the complex was consistent with the distribution data up to 3 h. The complex can be a possible in vivo generator compound for PET imaging in CXCR4 positive tumors.     

Design and evaluation of folate-appended methyl-��-cyclodextrin as a new antitumor agent

Methyl-??-cyclodextrin (M-??-CyD) is widely used as a raft disrupting agent through extraction of cholesterol from lipid rafts which are highly expressed in cell membranes of tumor cells, but it does not have tumor cell-selective action. Meanwhile, the widespread use of folic acid (FA) as a tumor-targeting ligand has been known, because folate receptor (FR) overexpresses in various kinds of epithelial tumor cells. In the present study, in order to obtain more tumor cell-selectivity and antitumor activity of M-??-CyD, we designed folate-appended M-??-CyD (FA-M-??-CyD), and evaluated its physicochemical properties and antitumor activity. The ¹H-NMR study demonstrated that FA-M-??-CyD having average degree of substitution of FA (DSF) of 1.0 was prepared. In addition, FA-M-??-CyD (DSF 1.0) was found to be amorphous in a solid state and surface-active. Importantly, FA-M-??-CyD (DSF 1.0) had potent cytotoxicity, compared to M-??-CyD in KB cells, but not in A549 cells. These results suggest that FA-M-??-CyD (DSF 1.0) has the potential as a novel antitumor agent.     

Complexo-titrimetric determination of mercury using hexahydropyrimidine-2-thione as a selective masking agent

A simple, rapid, accurate and selective complexometric method is proposed for the determina-tion of mercury(Ⅱ). Mercury(Ⅱ) is first complexed with a known excess of EDTA and the surplusEDTA is back-titrated at pH 5. 0--6. 0 with lead nitrate, xylenol orange being used as indicator. Hexa-hydropyrimidine-2-thione (HPT) is then added to displace EDTA from the Hg-EDTA complex quan-titatively and the EDTA released is titrated with lead nitrate. Reproducible and accurate results areobtained for 2--55 mg of mercury, with a relative error of less than 0. 5% and standard deviation ofless than 0.04.     

Preparation and in vivo imaging of a novel potential αvβ3 targeting PET/MRI dual-modal imaging agent

Journal of Radioanalytical and Nuclear Chemistry - Multi-modal biomedical imaging has played an essential role in tumor diagnosis. However, constructing a multi-modal imaging contrast agent with...