Potentiometric and Spectral Investigations of Anhydrotetracycline and Its Metal-Ion Complexes

Stoel, L. J.; Newman, E. C.; Asleson, G. L.; Frank, C. W.

doi:10.1002/jps.2600651225

Cited by 14 publications

(14 citation statements)

References 9 publications

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“…AHTC was synthesised using the following procedure 12) : a solution of 2-propanol (20.2 ml), methanol (1.5 ml) and concentrated hydrochloric acid (7.2 ml) was added to tetracycline hydrochloric (2.3975 g). After refluxing for 20 min, the resulting yellow precipitate was filtered, washed with 2-propanol (3ϫ10 ml) and dried under vacuum for 2.5 h. The crude product was then refluxed in benzene (250 ml).…”

Section: Methodsmentioning

confidence: 99%

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Binding of the Highly Toxic Tetracycline Derivative, Anhydrotetracycline, to Bovine Serum Albumin

Burgos

Fernández

Celej

et al. 2011

Biological & Pharmaceutical Bulletin

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Tetracycline (TC) derivatives comprise a group of bacteriostatic antibiotics extensively used in human and veterinary medicine and in acquaculture, and as animal growth promoters due to their safe toxicological profile.1) More recently, they have been proposed as anti-amyloidogenic drugs since they can interfere with protein conformational changes and self-assemblies associated with protein misfolding and deposition diseases. 2-4)Despite their popular use, TC derivatives are highly unstable and some degradation products formed during the storage or normal use of the drugs are pharmacologically toxic or inactive compounds.5) Anhydrotetracycline (AHTC) is one of the major degradation products of TC that has been linked to several side effects of the drug, e.g., cutaneous phototoxicity 6) and Fanconi-type syndrome. 7) AHTC has also proven to be more toxic than TC against environmentally relevant bacteria. 8)AHTC can be produced by dehydration in acid media, 5,8) by photolysis in mild reducing conditions 6,9,10) or during high-temperature treatments.11) Removal of a water molecule from the C5a-C6 positions of TC by treatment with warm mineral acid gives the anhydroderivative (Fig. 1).12) Dehydration leads to significant changes in aromatization and planarity of the tetracyclic moiety, 13,14) showing variations in potency, 15) mechanism of action 1) and lipophilicity 16,17) as compared to the parent compound. Changes in chemical configuration can also modulate the interaction of drugs with serum proteins. 18)Serum albumins are the main carriers of physiological metabolites and pharmacological drugs in blood. Protein binding has a significant impact on the pharmacokinetics and biological activity of drugs and modulates the toxicity of bound substances, attenuates adverse reactions and prolongs the in vivo half-life of therapeutic agents. 18-21)The facts outlined above prompted us to investigate the interaction of AHTC with bovine serum albumin (BSA) using three biophysical techniques. Binding affinity and number of interacting ligands were assessed by fluorimetric titration. . Drug binding was enthalpically and entropically driven and seemed to involve hydrophobic interactions. AHTC fluorescence enhancement and hypsochromic shifts observed upon binding suggested a low-polarity location excluded from water for the bound drug. Our data are useful for evaluating the biodisponibility of the pharmacophore and the dynamic distribution of the toxic derivative.

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Section: Methodsmentioning

confidence: 99%

“…1). 12) Dehydration leads to significant changes in aromatization and planarity of the tetracyclic moiety, 13,14) showing variations in potency, 15) mechanism of action 1) and lipophilicity 16,17) as compared to the parent compound. Changes in chemical configuration can also modulate the interaction of drugs with serum proteins.…”

mentioning

confidence: 99%

Binding of the Highly Toxic Tetracycline Derivative, Anhydrotetracycline, to Bovine Serum Albumin

Burgos

Fernández

Celej

et al. 2011

Biological & Pharmaceutical Bulletin

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“…1. Solid anhydrotetracycline hydrochloride was synthesized from tetracycline hydrochloride (Fluka) following the same methodology reported in [22]. pH values were adjusted using concentrated NaHO (Cicarelli, p.a.)…”

Section: Methodsmentioning

confidence: 99%

Transfer of tetracyclines across the H2O|1,2-dichloroethane interface: Analysis of degraded products in strong acid and alkaline solutions

Fernández

Dassie

2005

Journal of Electroanalytical Chemistry

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“…Fig. 1 shows the structure of tetracycline (TC) and anhydrotetracycline (AhTC), and the schematic representation of water removal from the C5a-C6 positions of tetracycline to give the anhydroderivative in acid media [3]. This figure also shows the acid groups, the known values for the acid dissociation constants, and the abbreviations referred to in this study for the compounds used.…”

Section: Introductionmentioning

confidence: 97%

“…Among the main degradation products that have been separated and identified, some are toxic or pharmacologically inactive. Anhydrotetracycline is one of the major toxic degradation products of tetracycline in acid media [1,2], by photolysis in mild reducing conditions [3][4][5] and it has known cutaneous phototoxicity [3]. The formation of anhydrotetracycline during a high-temperature treatment of animal-derived feed contaminated with tetracycline was also reported [6].…”

Section: Introductionmentioning

confidence: 99%

Electroanalytical procedure to resolve a sample solution containing tetracycline and its toxic degraded product: Anhydrotetracycline

Fernández

Dassie

2008

Journal of Electroanalytical Chemistry

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Potentiometric and Spectral Investigations of Anhydrotetracycline and Its Metal-Ion Complexes

Cited by 14 publications

References 9 publications

Binding of the Highly Toxic Tetracycline Derivative, Anhydrotetracycline, to Bovine Serum Albumin

Binding of the Highly Toxic Tetracycline Derivative, Anhydrotetracycline, to Bovine Serum Albumin

Transfer of tetracyclines across the H2O|1,2-dichloroethane interface: Analysis of degraded products in strong acid and alkaline solutions

Electroanalytical procedure to resolve a sample solution containing tetracycline and its toxic degraded product: Anhydrotetracycline

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