Conjugates of Desferrioxamine B (DFOB) with Derivatives of Adamantane or with Orally Available Chelators as Potential Agents for Treating Iron Overload

Abstract

Desferrioxamine B (DFOB) conjugates with adamantane-1-carboxylic acid, 3-hydroxyadamantane-1-carboxylic acid, 3,5-dimethyladamantane-1-carboxylic acid, adamantane-1-acetic acid, 4-methylphenoxyacetic acid, 3-hydroxy-2-methyl-4-oxo-1-pyridineacetic acid (N-acetic acid derivative of deferiprone), or 4-[3,5-bis(2-hydroxyphenyl)-1,2,4-triazol-1-yl]benzoic acid (deferasirox) were prepared and the integrity of Fe(III) binding of the compounds was established from electrospray ionization mass spectrometry and RP-HPLC measurements. The extent of intracellular (59)Fe mobilized by the DFOB-3,5-dimethyladamantane-1-carboxylic acid adduct was 3-fold greater than DFOB alone, and the IC(50) value of this adduct was 6- or 15-fold greater than DFOB in two different cell types. The relationship between logP and (59)Fe mobilization for the DFOB conjugates showed that maximal mobilization of intracellular (59)Fe occurred at a logP value approximately 2.3. This parameter, rather than the affinity for Fe(III), appears to influence the extent of intracellular (59)Fe mobilization. The low toxicity-high Fe mobilization efficacy of selected adamantane-based DFOB conjugates underscores the potential of these compounds to treat iron overload disease in patients with transfusional-dependent disorders such as beta-thalassemia.

Sickle Cell Disease – Current Treatment and New Therapeutical Approaches

“…The in vivo activities of these inhibitors include: a) the regulation of the arterial blood pressure; b) increased vascular resistance; c) the regression of atherosclerotic coronary lesions; d) the prevention of diabetes development; e) neurological repair; f) reduced formation of β-myeloid aggregates; and g) the inhibition of tumor growth, progression, and metastasis [98][99][100][101][102][103][104][105].…”

Reductometric Titration and Quantum Chemical Study of Oxalohydroxamic Acid for Determination of Manganese in Ores and Alloys

“…Extensive works have been carried out on their synthesis [1], complexation with metal ions [2], gravimetry [3], colorimetry [4], kinetics [5][6][7][8][9], spectrophotometry [10] and medical applications [11][12][13][14]. Benzohydroxamic acid was used as a reductometric titrant for determination of manganese, chromium [15] and cerium, uranium [16].…”

Hydroxamic Acids as a Reductometric Titrants: Determination of Cerium in Alloys

“…Extensive works have been carried out on their synthesis 1 , complexation with metal ions 2 , gravimetry 3 , colorimetry 4 , kinetics [5][6][7][8][9][10] , spectrophotometry 11 and medical applications [12][13][14][15] . Benzohydroxamic acid (BHA) was used as a reductometric titrant for determination of Mn, Cr 16 and Ce, U 17 .…”