Lipoamino acid conjugates of methotrexate with antitumor activity

R Pignatello; G Jansen; I Kathmann; G Puglisi; I Toth

doi:https://doi.org/10.1021/js970194p

Lipoamino acid conjugates of methotrexate with antitumor activity

R Pignatello, G Jansen, I Kathmann, G Puglisi, I Toth

Research output: Contribution to journal › Article › Academic › peer-review

25 Citations (Scopus)

Abstract

The synthesis, characterization, and in vitro antitumor activity against a wild and a transport-resistant CCRF-CEM cell line is described for a series of alpha,gamma-bisamide lipoamino acid and oligomer conjugates of methotrexate. The influence of the lipophilicity of the conjugates on the cytotoxicity and the dihydrofolate reductase inhibition was investigated. All compounds were more active than their fatty acid conjugate analogues. Compound le with a 12-carbon atom aliphatic side chain showed the highest in vitro activity.

Original language	English
Pages (from-to)	367-71
Number of pages	5
Journal	European journal of pharmaceutical sciences
Volume	87
Issue number	3
DOIs	https://doi.org/10.1021/js970194p
Publication status	Published - Mar 1998

Keywords

Amino Acids/chemistry
Antineoplastic Agents/chemistry
Cell Line
Chromatography, High Pressure Liquid
Folic Acid Antagonists/chemistry
Humans
Methotrexate/chemistry
Tetrahydrofolate Dehydrogenase/metabolism

Access to Document

https://doi.org/10.1021/js970194p

Cite this

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title = "Lipoamino acid conjugates of methotrexate with antitumor activity",

abstract = "The synthesis, characterization, and in vitro antitumor activity against a wild and a transport-resistant CCRF-CEM cell line is described for a series of alpha,gamma-bisamide lipoamino acid and oligomer conjugates of methotrexate. The influence of the lipophilicity of the conjugates on the cytotoxicity and the dihydrofolate reductase inhibition was investigated. All compounds were more active than their fatty acid conjugate analogues. Compound le with a 12-carbon atom aliphatic side chain showed the highest in vitro activity.",

keywords = "Amino Acids/chemistry, Antineoplastic Agents/chemistry, Cell Line, Chromatography, High Pressure Liquid, Folic Acid Antagonists/chemistry, Humans, Methotrexate/chemistry, Tetrahydrofolate Dehydrogenase/metabolism",

author = "R Pignatello and G Jansen and I Kathmann and G Puglisi and I Toth",

year = "1998",

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doi = "https://doi.org/10.1021/js970194p",

language = "English",

volume = "87",

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journal = "European journal of pharmaceutical sciences",

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T1 - Lipoamino acid conjugates of methotrexate with antitumor activity

AU - Pignatello, R

AU - Jansen, G

AU - Kathmann, I

AU - Puglisi, G

AU - Toth, I

PY - 1998/3

Y1 - 1998/3

N2 - The synthesis, characterization, and in vitro antitumor activity against a wild and a transport-resistant CCRF-CEM cell line is described for a series of alpha,gamma-bisamide lipoamino acid and oligomer conjugates of methotrexate. The influence of the lipophilicity of the conjugates on the cytotoxicity and the dihydrofolate reductase inhibition was investigated. All compounds were more active than their fatty acid conjugate analogues. Compound le with a 12-carbon atom aliphatic side chain showed the highest in vitro activity.

AB - The synthesis, characterization, and in vitro antitumor activity against a wild and a transport-resistant CCRF-CEM cell line is described for a series of alpha,gamma-bisamide lipoamino acid and oligomer conjugates of methotrexate. The influence of the lipophilicity of the conjugates on the cytotoxicity and the dihydrofolate reductase inhibition was investigated. All compounds were more active than their fatty acid conjugate analogues. Compound le with a 12-carbon atom aliphatic side chain showed the highest in vitro activity.

KW - Amino Acids/chemistry

KW - Antineoplastic Agents/chemistry

KW - Cell Line

KW - Chromatography, High Pressure Liquid

KW - Folic Acid Antagonists/chemistry

KW - Humans

KW - Methotrexate/chemistry

KW - Tetrahydrofolate Dehydrogenase/metabolism

U2 - https://doi.org/10.1021/js970194p

DO - https://doi.org/10.1021/js970194p

M3 - Article

C2 - 9523991

SN - 0022-3549

VL - 87

SP - 367

EP - 371

JO - European journal of pharmaceutical sciences

JF - European journal of pharmaceutical sciences

IS - 3

ER -