The use of metallocenic esters of n-hydroxysuccinimide for metallohapten synthesis

Different organometallic markers have been described in a new technique for the labelling of many drugs. Thus metallocenic esters of [M = (;CO)₃CrC₆H₅?; (;CO)₃CrC₆H₅?(;CH₂)₃?; η-C₅H₅?FeC₅H₄?; (;CO)₃MnηC₅H₄?; (;CO)₃Mn?ηC₅H₄COCH₂CH₂?; ηC₅H₄(;ηC₅H₅)Co⁺PF^?₆] react with primary or secondary amine drugs [DRUG?NHR] for a psychostimulant drug: amphetamine; tricyclic antidepressants—desipramine and nortriptyline; a vasodilator—histamine; an adrenergic substance—norfenefrine; and for a central stimulant—meth-amphetamine, to give the metallohaptens MCON(;R)—DRUG. All these compounds have been fully characterized by different analytical methods and have potentialities for biological assays. This synthetic route was found better than one presented previously which utilized the metallocenic acid chloride MCOCI as intermediate, and could be proposed as a general synthetic route for labelling biological compounds which possess an amino group.     

Optically active 2-cymantrenyloxazolines: synthesis and regioselective metallation

Three optically active oxazolines with a cymantrenyl substituent at position 2 of the heterocycle have been prepared. Metallation of these compounds withn-BuLi proceeds only at the two diastereotopic - and '-positions of the Cp-ring to an equal extent. The dependence of the sign of Cotton effect in the region of 300–350 nm upon the absolute configuration of chiral centers remote from the Cp-ring has been demonstrated.Translated fromIzvestiya Akademii Nauk, Seriya Khimicheskaya, No. 1, pp. 182–183, January, 1993.     

Stir bar sorptive extraction for central nervous system drugs from biological fluids

A review with 75 references is presented that deals with the reported methods for analysis of some important central nervous system (CNS) drugs in biological fluids utilizing stir bar sorptive extraction (SBSE) technique covering the years from 2000 to 2008. The theoretical aspects of SBSE, as well as an significant number of applications have been published, showing the advantages of this technique over the classical extraction techniques (liquid–liquid extraction (LLE) and solid-phase extraction (SFE). In this review, recent SBSE developments and a focus on the development of new instrumental approaches and sorbent phases are presented.     

Using HPLC for the determination of platinum drugs in biological matrixes after derivatization with diethyldithiocarbamate

Challenges and pitfalls in the application of diethyldithiocarbamate derivatization for LC analysis of cisplatin and oxaliplatin, as well as the suitability of this method for different biological matrices with implications for use in routine practice have been identified. The LC of platinum drugs presents a significant challenge. They are polar compounds with poor retention on reverse phase packings. Cisplatin also exhibits poor absorption in UV and ionization in mass spectrometry. Therefore, we developed and optimized a derivatization approach for the LC analysis of total platinum in plasma, plasma ultrafiltrate, peritoneal fluid, and urine. Derivatization in urine proved to be difficult due to the complexity of the matrix, and extended testing was required. Our results highlight the important issues affecting the efficiency, reliability, and suitability of platinum drug derivatization. Although precolumn derivatization is less selective than its postcolumn counterpart, the application of precolumn derivatization is a simple, rapid, and universal approach for the determination of platinum drugs by HPLC. One of its major advantages is that it allows a more affordable analysis using UV detection without the need for additional high-end instrumentation such as a MS detector.     

功能化氧化锌纳米棒放大电化学免疫分析乳制品中大肠杆菌的研究

将检测抗体(dAb)和二茂铁甲酸(FCA)固载于二氧化硅修饰的氧化锌(Zn O@Si O2)表面制备纳米复合材料标记物({dAb-Zn O-FCA}),并将其用于放大电化学免疫分析乳制品中的大肠杆菌(E.coli)。在{dAbZn O-FCA}中,检测抗体用于免疫结合大肠杆菌,二茂铁甲酸作为电活性物质产生电流信号。采用"三明治"免疫分析模式,基于二茂铁甲酸产生的电流信号与大肠杆菌浓度之间的线性关系实现了对大肠杆菌的检测。实验结果表明,二茂铁甲酸产生的电流信号与大肠杆菌浓度的对数在2.0×102~2.0×106cfu/m L范围内呈良好线性关系,检出限(S/N=3)为100 cfu/m L。利用该电化学免疫分析方法对乳制品进行了大肠杆菌的加标回收实验,回收率为95.8%~105%。     

A review on synthesis of antiviral drugs,in silico studies and their toxicity

Viruses have been around us for a long period of time; they are reported to affect humans, animals and plant at cellular level by using host's body to dwell and reproduce. The spread of HIV was reported in 1981 and created a global threat to public health. In the areas of basic virology, immunology and pathogenesis of HIV/AIDS, the development of antiretroviral medicines and significant progress has been made in recent years. Majority of these antiviral compounds have the potential to be used as HIV drugs, however they are frequently accompanied with some side effects. With the emergence of the COVID-19, human race is facing a new public health crisis and repurposing of antiviral drugs are being considered to block the function of Mpro of the new corona virus (SARS-CoV-2). This review covers the information related to the synthesis of various types of antiviral drugs and their toxicity. Some of these are used as repurposing drugs to cure patients suffering from other diseases/ infections. Therefore, information for in Silico studies of these antiviral drugs is incorporated. In brief, this review is focused on synthesis of different types of antiviral drugs, their repurposing role as well as toxicity.     

The use of plasmatic acceptors as specific ligands in affinity chromatography cleanup of veterinary drugs from biological matrices

Bovine α₁-acid glycoprotein (bAAG) and bovine serum albumin (BSA) are plasmatic acceptors working as carriers by the specific and reversible binding of several drugs in vivo. We synthesized affinity columns by coupling bAAG and BSA to an activated chromatographic support through their carbohydrate moieties, to preserve protein tertiary structure and, consequently, to improve the biological activity in vitro. The bAAG and BSA affinity columns were used to study the binding of acidic and basic drugs. Moreover, a purification strategy was developed for the cleanup of drug residues from biological matrices and foods, prior to screening and/or confirmatory analysis, on the basis of the specific molecular recognition between the protein and the drug. The aim of this work was to test the potency of bAAG- and BSA-based affinity chromatography to bind some veterinary drugs and purify them in the context of the official control of animal products. The efficiency of these homemade affinity columns in minimising matrix interference and in selective cleanup of different classes of substances was reported and discussed. Figure “Coupling strategies in synthesizing plasmatic acceptor affinity columns: the covalent coupling of bAAG and BSA through their carbohydrate moiety allows one to preserve the gross tertiary structure of the protein and thus its biological activity, whereas coupling through the ε-amine group of lysine residues can reduce the interactions with the binding sites of the plasmatic acceptor.”     

Thyroid hormone synthesis and anti-thyroid drugs: A bioinorganic chemistry approach

Hydrogen peroxide, generated by thyroid oxidase enzymes, is a crucial substrate for the thyroid peroxidase (TPO)-catalysed biosynthesis of thyroid hormones, thyroxine (T4) and triiodothyronine (T3) in the thyroid gland. It is believed that the H₂O₂ generation is a limiting step in thyroid hormone synthesis. Therefore, the control of hydrogen peroxide concentration is one of the possible mechanisms for the inhibition of thyroid hormone biosynthesis. The inhibition of thyroid hormone synthesis is required for the treatment of hyperthyroidism and this can be achieved by one or more anti-thyroid drugs. The most widely used anti-thyroid drug methimazole (MMI) inhibits the production of thyroid hormones by irreversibly inactivating the enzyme TPO. Our studies show that the replacement of sulphur in MMI by selenium leads to a selone, which exists predominantly in its zwitterionic form. In contrast to the sulphur drug, the selenium analogue (MSeI) reversibly inhibits the peroxidase-catalysed oxidation and iodination reactions. Theoretical studies on MSeI reveal that the selenium atom in this compound carries a large negative charge. The carbon-selenium bond length in MSeI is found to be close to single-bond length. As the selenium atom exhibits a large nucleophilic character, the selenium analogue of MMI may scavenge the hydrogen peroxide present in the thyroid cells, which may lead to a reversible inhibition of thyroid hormone biosynthesis.     

Novel silicon-containing drugs derived from the indomethacin scaffold: Synthesis, characterization and evaluation of biological activity

Synthesis, spectroscopic characterization and in vitro pharmacological and cancer cell growth inhibitory activity studies of new silicon-containing compounds based on the indomethacin scaffold are now reported. Amidation of the indomethacin carboxylate group using amino-functional silanes generated a series of novel lipophilic derivatives of indomethacin. The pharmacological activity of these derivatives tested against human recombinant cyclooxygenase-1 and 2 demonstrated that the silicon-containing derivatives are cyclooxygenase-2 (COX-2) selective. The silicon-containing amides of indomethacin demonstrated in vitro growth inhibitory activity against human MiaPaCa-2 pancreatic carcinoma cells at low μM concentrations. The 3a and 3c derivatives exhibited the most potent in vitro antiproliferative activity, with IC₅₀ <6.0 μM, compared to unmodified indomethacin having an IC₅₀100 μM. We dedicate this paper to Prof. Mitsuo Kira, outstanding organosilicon chemist and valued friend.     

Electroanalysis of antitubercular drugs in pharmaceutical dosage forms and biological fluids: A review

Tuberculosis remains a major global public health problem. Given the need for extensive analysis of antitubercular drugs, the development of sensitive, reliable and facile analytical methods to determine these compounds becomes necessary. Electrochemical techniques have inherent advantages over other well-established analytical methods, this review aiming to provide an updated overview of the latest trends (from 2006 till date) in the voltammetric determination of antitubercular drugs. Furthermore, the advantages and limitations of these methods are critically discussed. The review reveals that in spite of using a variety of chemically modified electrodes to determine antitubercular drugs, there is still a dearth of applicability of the voltammetric methods to quantify these compounds in human body fluids, especially in blood plasma.     

Homogeneous time-resolved fluorescence assays for the detection of activity and inhibition of phosphatase enzymes employing phosphorescently labeled peptide substrates

A rapid, homogenous, antibody-free assay for phosphatase enzymes was developed using the phosphorescent platinum (II)-coproporphyrin label (PtCP) and time-resolved fluorescent detection. An internally quenched decameric peptide substrate containing a phospho-tyrosine residue, labeled with PtCP-maleimide and dabcyl-NHS at its termini was designed. Phosphatase catalysed dephosphorylation of the substrate resulted in a minor increase in PtCP signal, while subsequent cleavage by chymotrypsin at the dephosphorylated Tyr-Leu site provided a 3.5 fold enhancement of PtCP phosphorescence. This phosphorescence phosphatase enhancement assay was optimized to a 96 well plate format with detection on a commercial TR-F plate reader, and applied to measure the activity and inhibition of alkaline phosphatase, recombinant human CD45, and tyrosine phosphatases in Jurkat cell lysates within 40 min. Parameters of these enzymatic reactions such as K_m's, limits of detection (L.O.D's) and IC₅₀ values for the non-specific inhibitor sodium orthovanadate were also determined.     

Magnetic microcapsules for targeted delivery of anticancer drugs

To achieve targeted distribution of anticancer drugs with sustained activity, ferromagnetic ethylcellulose microcapsules containing an anticancer drug, mitomycin C (FM-MMC-mc), were prepared by a method based on phase separation principles. Two prototypes of FM-MMC-mc were made: one with the drug as the core and zinc ferrite on its capsular surface (outer type); the other with both the drug and zinc ferrite as the core (inner type). Both preparations provided a sustained-release property and a sensitive response to conventional magnetic force, although certain differences in the release rate of drug, magnetic responsiveness, and particle size were found between the two dosage forms. Animal studies showed that the magnetic microcapsules could be magnetically controlled in the artery and urinary bladder. VX2 tumors in the rabbit hind limb and urinary bladder were successfully treated with magnetic control of FM-MMC-mc. Pharmacokinetic study revealed that the targeting of the microcapsules markedly enhanced the drug absorption into the surrounding tissues for a prolonged period of time. The results indicate the feasibility and effectiveness of the magnetic microcapsules as a targeted drug delivery system.     

Fully automatic simultaneous multiple peptide synthesis in micromolar scale - rapid synthesis of series of peptides for screening in biological assays.

A new method of simultaneous multiple peptide syntheses on polystyrene support in the wells of microtiterplates is illustrated by the syntheses of 31 overlapping segments of endothelin. All reagent and solvent handling is automatically performed by a freely programmable robotic sample processor.     

Characteristics of the thermal decomposition of antituberculous drugs

The thermal decomposition of antituberculous drugs-ethambutol (base and dihydrochloride), isoniazid, ethionamid and pyrazinamid has been studied by DTA, TG and DTG techniques. General remarks have been made on their thermal destruction. The effect of sample size over the range 20–200 mg and heating rate over the range 3–15 deg·min^?1 on the thermal degradation has also been investigated. Moreover, based on the Kissinger’s equation, the values of the kinetic parameters were determined.     

Polyoxomolybdate368 /polyaniline nanocomposite as a novel fiber for solid‐phase microextraction of antidepressant drugs in biological samples

A novel solid‐phase microextraction fiber was synthesized by coating a stainless steel wire with polyoxomolybdate₃₆₈/polyaniline as a sorbent aimed at extraction of amitriptyline, nortriptyline, and doxepin as antidepressant drugs from urine and blood samples. The polyoxomolybdate₃₆₈/polyaniline composite coating was applied using electropolymerization process under constant potential. This composition leads to enhanced extraction efficiency of the fiber. Scanning electron microscopy images show that huge three‐dimensional structures of polyoxomolybdate₃₆₈ in composite induced more non‐smooth and porous fiber. In order to optimize of the extraction process, a series of variables including concentration of the composite materials, coating thickness, pH, extraction time, salt addition, and stirring rate was investigated and optimum conditions were determined. Analysis of surface morphology and chemical composition was performed. High‐performance liquid chromatography was used for separation and evaluation of mentioned antidepressant drugs from the matrixes. The experiments indicated a detection limits of <0.2 ng/L and a linear dynamic range of 0.3–100 ng/L (R² > 0.994). The relative recovery values were found to be in the range of 92–98%. It was concluded that the purposed fiber is highly efficient in analyzing traces of antidepressant drugs in urine and blood.     

Ultrasound-assisted emulsification microextraction based on solidification of floating organic droplet combined with HPLC-UV for the analysis of antidepressant drugs in biological samples

Ultrasound-assisted emulsification microextraction based on the solidification of floating organic droplet combined with high-performance liquid chromatography-ultra violet (HPLC-UV) detection was applied for the extraction and determination of fluoxetine, citalopram, and venlafaxine as antidepressants drugs in biological samples. In total, 30 μL of undecanol was injected slowly into a glass-centrifuge tube containing 5 mL alkaline sample solution that was located inside the ultrasonic water bath. The formed emulsion was centrifuged and the fine droplets of solvent were floated at the top of the test tube. The test tube was then cooled in an ice bath and the solidified solvent transferred into a conical vial; it melted quickly at room temperature. Then the analysis of the extracts was carried out by high-performance liquid chromatography. Under optimal conditions, the preconcentration factors were between 174 and 316. Detection limits (LODs) of 3 μg/L were obtained and the calibration graphs were linear within the range of 10-1000 μg/L. Finally, the feasibility of the proposed method was successfully confirmed by extraction and determination of the antidepressant drugs in human urine and plasma samples in the range of microgram per liter and suitable results were obtained.     

Development of colloidal gold-based immumochromatographic assay for the rapid detection of medroxyprogesterone acetate residues in biological materials

A competitive colloidal gold-based immunoassay in lateral-flow format for the rapid detection of medroxyprogesterone acetate (MPA) in biological materials was developed. A nitro-cellulose membrane strip was separately coated with goat anti-rabbit IgG (control line) and MPA hapten-OVA conjugate (test line). Anti-MPA polyclonal antibody labelled with colloidal gold particles was first incubated with MPA. The limit of detection for lateral flow was 5?ng?g^?1 for detecting an MPA standard solution, and the limit of detection was 10?ng?mL^?1 for detecting the MPA spiked in pig urine and 10?ng?g^?1 for spiked in pig liver. The results were confirmed by high-performance liquid chromatography tandem mass spectrometry (HPLC/MS/MS) and indicated that there was a good agreement between both methods (R ²?=?0.976). The assay time for the test was less than 5?min, suitable for rapid testing on site.     

(2-Halogeno-5-pyridyl)dimethyl(oxiran-2-ylmethyl)silanes: New potential building blocks for the synthesis of silicon-containing drugs

(2-Fluoro-5-pyridyl)dimethyl(oxiran-2-ylmethyl)silane (1a) and (2-chloro-5-pyridyl)dimethyl(oxiran-2-ylmethyl)silane (1b) were prepared in two-step syntheses, starting from allylchlorodimethylsilane. Compounds 1a and 1b were characterized by elemental analyses and NMR studies. With the synthesis of 1a and 1b, new potential building blocks for the synthesis of silicon-containing drugs have been made accessible.