121031-00-3Relevant academic research and scientific papers
Development of a Redox-Sensitive Spermine Prodrug for the Potential Treatment of Snyder Robinson Syndrome
Phanstiel, Otto,Sekhar, Vandana,Tantak, Mukund P.,Tao, Xianzun,Zhai, R. Grace
, p. 15593 - 15607 (2021/11/16)
Snyder Robinson Syndrome (SRS) is a rare disease associated with a defective spermine synthase gene and low intracellular spermine levels. In this study, a spermine replacement therapy was developed using a spermine prodrug that enters cells via the polyamine transport system. The prodrug was comprised of three components: a redox-sensitive quinone "trigger", a "trimethyl lock (TML)"aryl "release mechanism", and spermine. The presence of spermine in the design facilitated uptake by the polyamine transport system. The quinone-TML motifs provided a redox-sensitive agent, which upon intracellular reduction generated a hydroquinone, which underwent intramolecular cyclization to release free spermine and a lactone byproduct. Rewardingly, most SRS fibroblasts treated with the prodrug revealed a significant increase in intracellular spermine. Administering the spermine prodrug through feeding in a Drosophila model of SRS showed significant beneficial effects. In summary, a spermine prodrug is developed and provides a lead compound for future spermine replacement therapy experiments.
SPERMINE PRO-DRUGS
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Paragraph 0011; 0025; 0067, (2021/01/26)
Disclosed herein are novel spermine prodrugs and methods of use for treating subjects exhibiting symptoms of a low spermine disorder. Also disclosed are methods of synthesizing spermine prodrugs. Compositions containing spermine prodrugs are also disclosed.
Reductive Lactonization of Strategically Methylated Quinone Propionic Acid Esters and Amides
Carpino, Louis A.,Triolo, Salvatore A,Berglund, Richard A
, p. 3303 - 3310 (2007/10/02)
It has been shown that the reduction of quinone propionic acid esters or amides bearing three methyl groups in the so-called "trialkyl lock" positions (o-, β-, β-positions) is accompanied by spontaneous lactonization with the release of alcohol or amine, respectively.A new convenient method is reported for introducing the β,β-dimethylpropionic acid side chain onto an appropriate hydroquinone nucleus via alkylative cyclization in methanesulfonic acid.Oxidation of the resulting lactone gives the quinone propionic acid, which can be converted by normal techniques to the corresponding ester or amide derivative.Initial model studies were carried out on pentamethylated systems 6 and 7.In order to make available quinones of varying redox potential or enhanced solubility in physiological media, methoxy- and amino-substituted quinones 10a, 10b, and 17a,b were synthesized.Upon reduction under mild conditions (Na2S2O4), all model esters or amides underwent reductive cyclization with loss of alcohol or amine.In the case of 7a the intermediate hydroquinone 19 could be isolated and its conversion to 4 with ejection of diethylamine followed by NMR techniques
