ArticleAmino acids2010
Metabolism of N-alkylated spermine analogues by polyamine and spermine oxidases.
Article in Amino acids, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers.
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Who cites it
7 citing papers in PubMed, 20 citations in OpenAlex.
- Polyamine-Derived Aminoaldehydes and Acrolein: Cytotoxicity, Reactivity and Analysis of the Induced Protein Modifications.Molecules (Basel, Switzerland) · 2023Review
- Exploring the activity of polyamine analogues on polyamine and spermine oxidase: methoctramine, a potent and selective inhibitor of polyamine oxidase.Journal of enzyme inhibition and medicinal chemistry · 2019Article
- Controlling the regioselectivity and stereospecificity of FAD-dependent polyamine oxidases with the use of amine-attached guide molecules as conformational modulators.Bioscience reports · 2018Article
- Cu(I)-catalyzed N,N'-diarylation of natural diamines and polyamines with aryl iodides.Beilstein journal of organic chemistry · 2015Article
- Pentamines as substrate for human spermine oxidase.Biological & pharmaceutical bulletin · 2013Article
- Article
- Current status of the polyamine research field.Methods in molecular biology (Clifton, N.J.) · 2011Review
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Authors and funding
8 authors at 4 institutions in 3 countries.
Funding
Abstract
N-alkylated polyamine analogues have potential as anticancer and antiparasitic drugs. However, their metabolism in the host has remained incompletely defined thus potentially limiting their utility. Here, we have studied the degradation of three different spermine analogues N,N'-bis-(3-ethylaminopropyl)butane-1,4-diamine (DESPM), N-(3-benzyl-aminopropyl)-N'-(3-ethylaminopropyl)butane-1,4-diamine (BnEtSPM) and N,N'-bis-(3-benzylaminopropyl)butane-1,4-diamine (DBSPM) and related mono-alkylated derivatives as substrates of recombinant human polyamine oxidase (APAO) and spermine oxidase (SMO). APAO and SMO metabolized DESPM to EtSPD [K(m(APAO)) = 10 microM, k(cat(APAO)) = 1.1 s(-1) and K(m(SMO)) = 28 microM, k(cat(SMO)) = 0.8 s(-1), respectively], metabolized BnEtSPM to EtSPD [K(m(APAO)) = 0.9 microM, k(cat(APAO)) = 1.1 s(-1) and K(m(SMO)) = 51 microM, k(cat(SMO)) = 0.4 s(-1), respectively], and metabolized DBSPM to BnSPD [K(m(APAO)) = 5.4 microM, k(cat(APAO)) = 2.0 s(-1) and K(m(SMO)) = 33 microM, k(cat(SMO)) = 0.3 s(-1), respectively]. Interestingly, mono-alkylated spermine derivatives were metabolized by APAO and SMO to SPD [EtSPM K(m(APAO)) = 16 microM, k(cat(APAO)) = 1.5 s(-1); K(m(SMO)) = 25 microM, k(cat(SMO)) = 8.2 s(-1); BnSPM K(m(APAO) )= 6.0 microM, k(cat(APAO)) = 2.8 s(-1); K(m(SMO)) = 19 muM, k(cat(SMO)) = 0.8 s(-1), respectively]. Surprisingly, EtSPD [K(m(APAO)) = 37 microM, k(cat(APAO)) = 0.1 s(-1); K(m(SMO)) = 48 microM, k(cat(SMO)) = 0.05 s(-1)] and BnSPD [K(m(APAO)) = 2.5 microM, k(cat(APAO)) = 3.5 s(-1); K(m(SMO)) = 60 microM, k(cat(SMO)) = 0.54 s(-1)] were metabolized to SPD by both the oxidases. Furthermore, we studied the degradation of DESPM, BnEtSPM or DBSPM in the DU145 prostate carcinoma cell line. The same major metabolites EtSPD and/or BnSPD were detected both in the culture medium and intracellularly after 48 h of culture. Moreover, EtSPM and BnSPM were detected from cell samples. Present data shows that inducible SMO parallel with APAO could play an important role in polyamine based drug action, i.e. degradation of parent drug and its metabolites, having significant impact on efficiency of these drugs, and hence for the development of novel N-alkylated polyamine analogues.
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