In vitro detoxification of cyclosarin (GF) by modified cyclodextrins (original) (raw)
Related papers
Journal of Pharmaceutical and Biomedical Analysis, 2016
The main goal of this review is to provide a comprehensive overview on the methods used for analysis of cyclodextrins (CDs) and CD-derivatives. The paper intends to act as a guide for the readers in looking around the classical and modern instrumental analytical methods suitable for identification, characterization and determination of CDs themselves, CDs in finished products or even in biological samples. At present, in the European and United States Pharmacopoeias, the three parent CDs and two synthetic derivatives, namely the (2-hydroxypropyl)-beta-CD and sulfobutylether-beta-CD Na salt are official. Besides these modified CDs, two other derivatives are approved as excipients in human pharmaceutical products: the (2-hydroxypropyl)-gamma-CD and the randomly methylated-beta-CD. Although most of the official analysis methods in the pharmacopoeias have been well used for decades, new aspects of the functional excipient CD characterization suggest a need to revisit compendial methods. Comparison of strengths and weaknesses of current official methods with new improved techniques intends to help analysts to decide on changing traditional analytical methods with improved new ones. This review also deals with the analytical aspects of the first single isomer CD derivative approved as a drug active (Sugammadex/Bridion ®) as well as analytical considerations of using CDs themselves as active pharmaceutical ingredients. Stability-indicating instrumental methods suitable to adequately follow chemical-and enzymatic degradation of CDs will also be discussed. Challenges in the determination of CDs in different biological matrices will be illustrated on real pharmaco-and toxicokinetic studies of CD-enabled drug formulations.
Beilstein Journal of Organic Chemistry, 2017
New derivatives of cyclodextrins were prepared in order to determine the relative importance of the structural key elements involved in the degradation of organophosphorus nerve agents. To avoid a competitive inclusion between the organophosphorus substrate and the iodosobenzoate group, responsible for its degradation, the latter group had to be covalently bound to the cyclodextrin scaffold. Although the presence of the α nucleophile iodosobenzoate was a determinant in the hydrolysis process, an imidazole group was added to get a synergistic effect towards the degradation of the agents. The degradation efficiency was found to be dependent on the relative position of the heterocycle towards the reactive group as well as on the nature of the organophosphorus derivative.
Curative Potential of Substances with Bioactive Properties to Alleviate Cd Toxicity: A Review
International Journal of Environmental Research and Public Health
Rapid urbanization and industrialization have led to alarming cadmium (Cd) pollution. Cd is a toxic heavy metal without any known physiological function in the organism, leading to severe health threat to the population. Cd has a long half-life (10–30 years) and thus it represents serious concern as it to a great extent accumulates in organs or organelles where it often causes irreversible damage. Moreover, Cd contamination might further lead to certain carcinogenic and non-carcinogenic health risks. Therefore, its negative effect on population health has to be minimalized. As Cd is able to enter the body through the air, water, soil, and food chain one possible way to defend and eliminate Cd toxicities is via dietary supplements that aim to eliminate the adverse effects of Cd to the organism. Naturally occurring bioactive compounds in food or medicinal plants with beneficial, mostly antioxidant, anti-inflammatory, anti-aging, or anti-tumorigenesis impact on the organism, have been ...
Journal of Pharmaceutical Sciences, 2004
NSC-281612 (4-[bis[2-[(methylsulfonyl)oxy]ethyl]amino]-2-methyl-benzaldehyde, 1), is a chemically unstable, poorly water soluble, experimental antineoplastic agent. The saturated solubility in water at 258C was determined as $30 mg/mL. In the pH range 2-11, 1 displayed pH-independent stability (t 50 was around 24 hr). However, an increase in the degradation rate was observed at pH 12. The hydrolysis of the methane sulfonate groups to the corresponding hydroxyl groups was the major degradation pathway in water in the absence of buffers and added halide ions. In phosphate buffer solutions without sodium chloride, phosphate degradants appear to be formed in addition to the mono-and dihydroxy degradants. Additional degradants, the mono-and dichloro degradation products, were formed when the ionic strength of the solution was adjusted with sodium chloride. When bromide and iodide ions were added, the corresponding monoand dihalides were formed. The chloro compounds subsequently underwent further degradation to the hydroxy products. A deuterium kinetic solvent isotope effect study showed that water was minimally involved in the rate-determining step. The addition of either (SBE) 7m-b-cyclodextrin (CD) or HP-b-CD resulted in a significant enhancement in drug solubility and stability. The apparent binding constants for HP-b-CD and (SBE) 7m-b-CD were 1,486 and 2,740 M À1 , respectively. The stability of 1 in the presence of 0.1 M HP-b-CD and (SBE) 7m-b-CD was enhanced 9-and 15-fold, respectively. Thus, (SBE) 7m-b-CD displayed better solubilization and stabilization efficacy than HP-b-CD.
Interactions of cyclodextrins and their derivatives with toxic organophosphorus compounds
Beilstein Journal of Organic Chemistry, 2016
The aim of this review is to provide an update on the current use of cyclodextrins against organophosphorus compound intoxications. Organophosphorus pesticides and nerve agents play a determinant role in the inhibition of cholinesterases. The cyclic structure of cyclodextrins and their toroidal shape are perfectly suitable to design new chemical scavengers able to trap and hydrolyze the organophosphorus compounds before they reach their biological target.
Carbohydrate Research, 1999
Following our recent study of the bromine oxidation, at neutral pH, of a-cyclodextrin, b-cyclodextrin, O-methylated b-cyclodextrins and sucrose, which yield ketone and carboxylic acid-containing materials in the oxidation products (M.E. Deary, D.M. Davies, Carbohydr. Res., 309 (1998) 17), we have extended the work to hydroxypropyla-cyclodextrin and hydroxypropyl-b-cyclodextrin. 13 C NMR analysis confirms the presence of ketone groups (l 207) in the oxidation products of both of these compounds. The continued ability of the products of these oxidations to complex p-nitrophenol demonstrates that ring integrity is maintained. The ketone-containing products are capable of catalysing the peroxomonosulfate (PMS) oxidation of a range of substrates including aryl alkyl sulfoxides, pyridine, 4-bromopyridine, aniline, 4-aminobenzoate, 4-bromoaniline and several amino acids, most probably by the formation of a more reactive cyclodextrin -dioxirane intermediate. A small degree of enantioselectivity is observed in the oxidation of (R)-(+)-and (S)-( −)-methyl p-tolyl sulfoxide by PMS in the presence of the keto derivative of hydroxypropyl-a-cyclodextrin, though not for the b analogue.
Molecules
Cyclodextrins (CDs) are cyclic oligosaccharides which can trap hydrophobic molecules and improve their chemical, physical, and biological properties. γ-CD showed the highest aqueous solubility with the largest cavity diameter among other CD types. The current study describes a direct and easy method for nucleophilic mono-aminos to be substituted with γ-CD and tested for their ability to host the guest curcumin (CUR) as a hydrophobic drug model. The mass spectrometry and NMR analyses showed the successful synthesis of three amino-modified γ-CDs: mono-6-amino-6-deoxy-cyclodextrine (γ-CD-NH2), mono-6-deoxy-6-ethanolamine-γ-cyclodextrine (γ-CD-NHCH2CH2OH), and mono-6-deoxy-6-aminoethylamino)-γ-cyclodextrin (γ-CD-NHCH2CH2NH2). These three amino-modified γ-CDs were proven to be able to host CUR as native γ-CDs with formation constants equal to 6.70 ± 1.02, 5.85 ± 0.80, and 8.98 ± 0.90 mM−1, respectively. Moreover, these amino-modified γ-CDs showed no significant toxicity against human der...
Inorganic Chemistry, 2005
The involvement of Cd(II) in toxic manifestations and pathological aberrations in lower and higher organisms entails interactions with low and high molecular mass biological targets. To understand the relevant chemistry in aqueous media, we have launched pH-dependent synthetic efforts targeting Cd(II) with the physiological ligand citric acid. Reactions of Cd(II) with citric acid upon the addition of NaOH at pH 2.5 and pyridine at pH 3 and the addition of ammonia at pH ∼7 led to the new complexes [Cd 3 (C 6 H 5 O 7) 2 (H 2 O) 5 ]‚H 2 O (1) and (NH 4)[Cd(C 6 H 5 O 7)(H 2 O)]‚H 2 O (2), respectively. Complexes 1 and 2 were characterized by elemental analysis, spectroscopy (FT-IR and NMR), and X-ray crystallography. Complex 1 crystallizes in the monoclinic space group P2 1 /n, with a) 18.035(6) Å, b) 10.279(4) Å, c) 12.565(4) Å,) 109.02(1)°, V) 2202(2) Å 3 , and Z) 4. Complex 2 crystallizes in the monoclinic space group P2 1 , with a) 9.686(4) Å, b) 8.484(4) Å, c) 7.035(3) Å,) 110.28(1)°, V) 542.3(4) Å 3 , and Z) 2. Complex 1 is a trinuclear assembly with the citrate ligand securing a stable metallacyclic ring around one Cd(II), with the terminal carboxylates spanning into the coordination sphere of two nearby Cd(II) ions. Complex 2 contains mononuclear units of Cd(II) bound by citrate in an overall coordination number of 8. In both 1 and 2, the participating citrates exhibit three different modes of coordination, thus projecting a distinct yet variable aqueous structural chemistry of Cd(II) with physiological substrates. The pH-dependent chemistry and its apparent structural diversity validate past solution speciation studies, projecting the existence of mononuclear species such as the one in the anion of 2. The spectroscopic and structural properties of 2 emphasize the significance of the information emerging from synthetic studies that otherwise would not have been revealed through conventional solution studies, while concurrently shedding light onto the linkage of the requisite chemistry with the potential biological toxicity of Cd(II).