THE TOXICITY OF o- AND p-FLUOROPHENYL-dl-ALANINES FOR THE RAT

Armstrong, Marvin D.; Lewis, Joy D.

doi:10.1016/s0021-9258(18)56149-4

Cited by 21 publications

References 7 publications

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Intracellular uptake and inhibitory activity of aromatic fluorinated amino acids in human breast cancer cells

et al. 2008

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Nonproteinogenic amino acids that either occur naturally or are synthesized chemically are becoming important tools in modern drug discovery. In this context, fluorinated amino acids have great potential in the development of novel pharmaceuticals and drugs. To assess whether different fluorinated aromatic amino acid analogues of phenylalanine, tyrosine, and tryptophan are potentially interesting as therapeutic drugs, we examined their cytostatic and cytotoxic effects on the growth of the human breast cancer cell line MCF-7. Of all the tested analogues L-4-fluorotryptophan, L-6-fluorotryptophan and L-p-fluorophenylalanine effectively and irreversibly inhibited cell growth with IC(50) values in the low micromolar range (3-15 microM). Additionally, using L-4-[14C]fluorotryptophan, and L-6-[14C]fluorotryptophan, we discovered that the cellular uptake of these fluorinated amino acids occurs through active transport with a 70-fold excess of intracellular over extracellular concentrations. We identified system L as the responsible amino acid transporter. Our findings fully support the idea that fluorinated aromatic amino acid analogues are promising chemotherapeutics with the potential for use in combination with classical cancer therapy, and as new cytotoxic drugs for certain tumor types such as melanoma.

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Intracellular uptake and inhibitory activity of aromatic fluorinated amino acids in human breast cancer cells

et al. 2008

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Fluor‐Derivate biogener aliphatischer Aminosäuren

Lettré

Wölcke

1967

Justus Liebigs Ann. Chem.

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Es werden Synthesen von DL-y.y'-Difluor-valin (6), DL-6.6'-Difluor-leucin (13) und DL-y-FIuor-(al1o)threonin (18) beschrieben. Die Darstellungen der bereits bekannten ~~-2-Amino-4-fluorbuttersaure (21) und des DL-P-Fluor-alanins (27) sind verbessert worden. Das Dipeptid DL-P-Fluor-alanyl-L-leucin (30) wird dargestellt. Fluor-Substitutionsprodukte naturlicher Substrate sind fur die Chemotherapie desKrebses von Interesse. Ersetzt man einzelne Wasserstoffatome in biogenen Substanzen durch Fluor, dessen Atomvolumen sich von dem des Wasserstoffs nur wenig unterscheidet, so entstehen isostere Verbindungen, die moglicherweise als Antimetaboliten wirksam sind.Das von Heidelberger h 2 ) beschriebene 5-Fluor-uracil und seine Derivate wirken wachstumshemmend auf Tumoren ; 2-Fluor-adenosin3) verlangsamt die Wachstumsgeschwindigkeit mancher maligner Gewebe. Auch Fluor-Derivate biogener Aminosauren sind schon auf ihre cytostatische Wirkung untersucht worden : Nach Armstrong und Lewis41 vermindern 0-und p-Fluor-phenylalanin die Wachstumsrate von Ratten. Rubinovitzs) beobachtete am Ehrlich-Ascitestumor in vitro, daB o-Fluor-phenylalanin den Einbau des Phenylalanins in Proteine stort.Fluor-Substitutionsprodukte aromatischer Aminosauren sind mit Hilfe der Schie mann-Reaktions) verhaltnismafiig gut zuganglich. Aus der Reihe der Mono-und Difluor-substituierten aliphatischen biogenen Aminosauren sind dagegen bislang nur wenige Vertreter bekannt.

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Effect of Acylated Amino Acids and Acylated Amino Acid Analogs on Microbial Antitumor Screen

Otani

Briley

1978

Journal of Pharmaceutical Sciences

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THE TOXICITY OF o- AND p-FLUOROPHENYL-dl-ALANINES FOR THE RAT

Cited by 21 publications

References 7 publications

Intracellular uptake and inhibitory activity of aromatic fluorinated amino acids in human breast cancer cells

Intracellular uptake and inhibitory activity of aromatic fluorinated amino acids in human breast cancer cells

Fluor‐Derivate biogener aliphatischer Aminosäuren

Effect of Acylated Amino Acids and Acylated Amino Acid Analogs on Microbial Antitumor Screen

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