21269-37-4Relevant academic research and scientific papers
Spectrophotometric determination of tiopronin in pharmaceutical samples by phosphorus molybdenum blue
Fan, Binglin,Wang, Yingling,Yang, Jie,Ni, Tianjun,Li, Quanmin
, p. 331 - 334 (2014)
A novel method is established for spectrophotometric determination of tiopronin by phosphorus molybdenum blue. It is based on the fact that PO 43- reacts with Mo7O246- in 0.47 mol/L H2SO4 solution to form a product of phosphorus-molybdenum heteropoly acid ([H2PMo12O 40]-) which is reduced to phosphorus molybdenum blue (H3PO4·10MoO3·Mo 2O5) by tiopronin. The absorbance of phosphorus molybdenum blue is measured at the absorption maximum of 730 nm and the amount of tiopronin can be determined based on this absorbance. Absorbance is linear with the concentration of tiopronin in the range of 1.6-40 μg/mL and the regression equation is A = -0.1193 + 0.01927c (μg/mL) with a correlation coefficient of 0.9989 and the apparent molar absorption coefficient of 3.14 × 103 L/(mol cm). The detection limit and the RSD are 1 μg/mL and 0.92 %, respectively. Thus, the method is validated and commonly available to determine tiopronin in pharmaceutical samples.
Kinetics and mechanism of reactions of the drug tiopronin with platinum(IV) complexes
Huo, Shuying,Shi, Hongmei,Liu, Dongzhi,Shen, Shigang,Zhang, Jiong,Song, Changying,Shi, Tiesheng
, p. 9 - 15 (2013)
Tiopronin, a synthetic thiol-containing drug being used in treatments of cystinuria and certain types of rare arthritis, is also a hepatoprotective and a detoxifying agent. Many analytical methods have been developed based on its redox chemistry with metal ions/complexes, but the kinetic and mechanistic aspects are poorly understood. In this work, the oxidation of tiopronin by cisplatin prodrug and a model compound, cis-[Pt(NH3) 2Cl4] and trans-[PtCl2(CN)4] 2 -, was investigated. The oxidation kinetics was followed by a stopped-flow spectrophotometer over a wide pH range under the pseudo first-order conditions of [Tiopronin][Pt(IV)]. Time-resolved spectra were also recorded for both Pt(IV) complexes, enabling to establish an overall second-order rate law: - d[Pt(IV)] / dt = k′[Tiopronin][Pt(IV)], where k′ pertains to observed second-order rate constants. Under the kinetic conditions, tiopronin was oxidized to form the tiopronin-disulfide exclusively as identified by mass spectrometry. A reaction mechanism was proposed, involving parallel reductions of the Pt(IV) complexes by the three protolytic tiopronin species as rate-determining steps. The rate constants for the rate-determining steps were derived. The fully deprotonated tiopronin is about 4 × 104 more reactive than its corresponding thiol form for both Pt(IV) complexes; the huge reactivity difference orchestrates closely with the fact that the nucleophilicity of thiolate is much higher than the corresponding thiol. Hence, the attack of the sulfur atom in thiol/thiolate of tiopronin on the axially-coordinated chloride in the Pt(IV) complexes is nucleophilic in nature in the rate-determining steps, resulting in a bridge formation and a subsequent bridged electron-transfer.
RETRACTED ARTICLE: Collateral sensitivity of multidrug-resistant cells to the orphan drug tiopronin
Goldsborough, Andrew S.,Handley, Misty D.,Dulcey, Andrés E.,Pluchino, Kristen M.,Kannan, Pavitra,Brimacombe, Kyle R.,Hall, Matthew D.,Griffiths, Gary,Gottesman, Michael M.
supporting information; experimental part, p. 4987 - 4997 (2011/10/01)
A major challenge in the treatment of cancer is multidrug resistance (MDR) that develops during chemotherapy. Here we demonstrate that tiopronin (1), a thiol-substituted N-propanoylglycine derivative, was selectively toxic to a series of cell lines expressing the drug efflux pump P-glycoprotein (P-gp, ABCB1) and MRP1 (ABCC1). Treatment of MDR cells with 1 led to instability of the ABCB1 mRNA and consequently a reduction in P-gp protein, despite functional assays demonstrating that tiopronin does not interact with P-gp. Long-term exposure of P-gp-expressing cells to 1 sensitized them to doxorubicin and paclitaxel, both P-gp substrates. Treatment of MRP1-overexpressing cells with tiopronin led to a significant reduction in MRP1 protein. Synthesis and screening of analogues of tiopronin demonstrated that the thiol functional group was essential for collateral sensitivity while substitution of the amino acid backbone altered but did not destroy specificity, pointing to future development of targeted analogues. This article not subject to U.S. Copyright. Published 2011 by the American Chemical Society.
