Induction of differentiation of leukemia cells in vitro by N-substituted amides, lactams, and 2-pyridones

Chau Der Li, Edward L. Schwartz, Sharon L. Mella, Lana S. Rittmann, Alan C. Sartorelli

Research output: Contribution to journalArticle

11 Citations (Scopus)

Abstract

N-Substituted amides, lactams, and 2-pyridones were examined for their ability to induce leukemic cell differentiation in vitro. These substituted amides were effective inducers of the differentiation of murine erythroleukemia (Friend) cells, as judged by the cellular accumulation of hemoglobin. N-Substitution increases the effectiveness of all classes of agents as inducers of maturation as judged by an increase in potency. N-Cyclohexylacetamide appeared to be a particularly effective compound, causing 92% of the population to synthesize hemoglobin at a concentration which was not inhibitory to cell replication. In the lactam series, an increase in ring size was paralleled by an increase in the potency of unsubstituted compounds, but ring size had less effect on N-substituted lactams. Increasing the chain length of the N-alkyl substituent had little additional effect on a series of lactam and 2-pyridone derivatives; however, some decrease in maximal induction occurred with butyl- and hexyl-substituted 2-pyridones. N-Isopropyl-2-pyridone, selected for further study, was as good an inducer of the HL60 human promyelocytic leukemia as it was of the Friend murine erythroleukemia.

Original languageEnglish (US)
Pages (from-to)1092-1094
Number of pages3
JournalJournal of Medicinal Chemistry
Volume24
Issue number9
StatePublished - 1981
Externally publishedYes

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Lactams
Amides
Cell Differentiation
Leukemia
Leukemia, Erythroblastic, Acute
Hemoglobins
Chain length
Substitution reactions
Derivatives
2-hydroxypyridine
In Vitro Techniques
Population

ASJC Scopus subject areas

  • Organic Chemistry

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Induction of differentiation of leukemia cells in vitro by N-substituted amides, lactams, and 2-pyridones. / Li, Chau Der; Schwartz, Edward L.; Mella, Sharon L.; Rittmann, Lana S.; Sartorelli, Alan C.

In: Journal of Medicinal Chemistry, Vol. 24, No. 9, 1981, p. 1092-1094.

Research output: Contribution to journalArticle

Li, Chau Der ; Schwartz, Edward L. ; Mella, Sharon L. ; Rittmann, Lana S. ; Sartorelli, Alan C. / Induction of differentiation of leukemia cells in vitro by N-substituted amides, lactams, and 2-pyridones. In: Journal of Medicinal Chemistry. 1981 ; Vol. 24, No. 9. pp. 1092-1094.
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AU - Schwartz, Edward L.

AU - Mella, Sharon L.

AU - Rittmann, Lana S.

AU - Sartorelli, Alan C.

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N2 - N-Substituted amides, lactams, and 2-pyridones were examined for their ability to induce leukemic cell differentiation in vitro. These substituted amides were effective inducers of the differentiation of murine erythroleukemia (Friend) cells, as judged by the cellular accumulation of hemoglobin. N-Substitution increases the effectiveness of all classes of agents as inducers of maturation as judged by an increase in potency. N-Cyclohexylacetamide appeared to be a particularly effective compound, causing 92% of the population to synthesize hemoglobin at a concentration which was not inhibitory to cell replication. In the lactam series, an increase in ring size was paralleled by an increase in the potency of unsubstituted compounds, but ring size had less effect on N-substituted lactams. Increasing the chain length of the N-alkyl substituent had little additional effect on a series of lactam and 2-pyridone derivatives; however, some decrease in maximal induction occurred with butyl- and hexyl-substituted 2-pyridones. N-Isopropyl-2-pyridone, selected for further study, was as good an inducer of the HL60 human promyelocytic leukemia as it was of the Friend murine erythroleukemia.

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