Derivatives of butyric acid as potential anti‐neoplastic agents

@article{Rephaeli1991DerivativesOB,
  title={Derivatives of butyric acid as potential anti‐neoplastic agents},
  author={A. Rephaeli and E. Rabizadeh and A. Aviram and M. Shaklai and M. Ruse and A. Nudelman},
  journal={International Journal of Cancer},
  year={1991},
  volume={49}
}
A novel derivative of butyric acid, pivalyloxymethyl butyrate (AN‐9) has been shown, in vitro, to: (a) induce cytodifferentiation and inhibit the proliferation of leukemic cells; (b) inhibit the growth and formation of Lewis lung carcinoma colonies in semi‐solid agar. AN‐9 affect cells at about 10‐fold lower concentration and at a faster rate than does butyric acid. The pivalyloxymethyl esters of propionic, isobutyric and valeric acids do not elicit effects similar to those of AN‐9, while the… Expand
Comparison between the effect of butyric acid and its prodrug pivaloyloxymethylbutyrate on histones hyperacetylation in an HL‐60 leukemic cell line
TLDR
It is shown that both AN‐9 and butyric acid caused a transient hyperacetylation of histones, which returned to basal levels after 6 and 12 hr, respectively, this activity precedes the induction of differentiation elicited by both agents. Expand
An anti-cancer derivative of butyric acid (pivalyloxmethyl buterate) and daunorubicin cooperatively prolong survival of mice inoculated with monocytic leukaemia cells.
TLDR
AN-9 as a single agent prolonged the survival of mice inoculated with Mm-A cells in a dose-dependent manner and administration of AN-9 plus daunorubicin (DNR) markedly prolonged their survival, suggesting that combination with AN- 9 and DNR entails an obvious therapeutic potential. Expand
Activity of pivaloyloxymethyl butyrate, a novel anticancer agent, on primary human tumor colony-forming units
TLDR
AN-9 is a novel differentiating agent with activity against colony-forming units derived from a variety of primary human tumors, including those that are considered relatively chemoresistant, and may thus provide a therapeutic alternative or addition to standard cytotoxic agents, if appropriate drug concentrations can be achieved in patients. Expand
Effect of the cytostatic butyric acid pro-drug, pivaloyloxymethyl butyrate, on the tumorigenicity of cancer cells
TLDR
It is demonstrated that AN-9 is a cytostatic but not cytotoxic agent in a myelomonocytic cell line (WEHI); thus, the cells were growth-arrested and differentiated. Expand
Butyric acid and pivaloyloxymethyl butyrate, AN-9, a novel butyric acid derivative, induce apoptosis in HL-60 cells
TLDR
It is shown that AN-9 and butyric acid induce cell death by apoptosis and that HL-60 cells that were induced to differentiate by preincubation with retinoic acid or low AN- 9 concentrations were more resistant to apoptosis, induced later by high concentrations of An-9, than were undifferentiated cells. Expand
Doxorubicin and a butyric acid derivative effectively reduce levels of BCL‐2 protein
in the cells of chronic lymphocytic
leukemia patient
TLDR
The combination of low concentrations of AN‐9 and doxorubicin more than additively enhanced apoptosis and reduced bcl‐2 levels in B‐CLL cultures which were resistant to An‐9. Expand
Role of butyric acid and its derivatives in the treatment of colorectal cancer and hemoglobinopathies.
TLDR
It is evident that continuous infusions of butyrate are required to improve the efficacy of the treatment, and the described hyperacetylation of histones and the induction of several immune or non-immune cell-activating mediators are consistent with the pleiotropic stimulatory effect of the agent. Expand
Synergistic cytotoxicity of artemisinin and sodium butyrate on human cancer cells.
TLDR
DHA in combination with butyric acid acts synergistically at low doses in killing cancer cells and may provide a less toxic, inexpensive and effective cancer chemotherapy. Expand
The selectivty and anti-metastatic activity of oral bioavailable butyric acid prodrugs
TLDR
In vivo, anti-metastatic activity was evaluated in a metastatic model of lung cancer in which Lewis lung carcinoma cells are injected intravenously into C57/BL mice and produce lung nodules and the good oral bioavailability of AN-7 was confirmed. Expand
A phase I study of pivaloyloxymethyl butyrate, a prodrug of the differentiating agent butyric acid, in patients with advanced solid malignancies.
TLDR
Dose escalation of AN-9 was limited by the maximum feasible volume of its intralipid formulation vehicle that could be administered safely on this schedule, resulting in a maximum deliverable dose of 3.3 g/m(2)/day. Expand
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References

SHOWING 1-10 OF 15 REFERENCES
Effect of polar organic compounds on leukemic cells: Butyrate‐induced partial remission of acute myelogenous leukemia in a child
TLDR
Organic agents that induce cell differentiation may provide additional reagents for the clinical management of selected cases of leukemia and butyrate was the most potent. Expand
Butyric acid: a small fatty acid with diverse biological functions.
TLDR
In vitro studies suggest that sodium butyrate may be useful in the management of neoplasms by causing selective cell death, and/or cell differentiation and by increasing the cell killing effect in conjuction with currently used tumor therapeutic agents. Expand
Effects of differing concentrations of sodium butyrate on 1,2-dimethylhydrazine-induced rat intestinal neoplasia.
TLDR
It is suggested that dietary butyrate has an important, possibly indirect, regulatory role in carcinogenesis associated with an experimental animal model of colonic neoplasia. Expand
Diet, butyric acid and differentiation of gastrointestinal tract tumours.
  • J. Jass
  • Biology, Medicine
  • Medical hypotheses
  • 1985
TLDR
Relatively low intracolonic levels of n-butyrate are associated with a low fibre diet and the presence of naturally occurring differentiating agents, such as n- butyrate, may modify the patterns of growth and differentiation of gastrointestinal tumours. Expand
Clinical pharmacology of sodium butyrate in patients with acute leukemia.
TLDR
A significant increase in peripheral blast cells was observed, whereas bone marrow cytologies before and after treatment did not reveal a significant change in blasts, and the apparent lack of clinical efficacy may be explained by the low plasma levels of sodium butyrate due to its short half-life in vivo. Expand
Butyric acid, a potent inducer of erythroid differentiation in cultured erythroleukemic cells
TLDR
Studies using a variety of analogues and metabolites suggest that the structural features of butyric acid are rather stringently required for induction of erythroid differentiation. Expand
Molecular analysis of sodium butyrate-induced growth arrest.
TLDR
Sodium butyrate-induced growth arrest of Swiss 3T3 cells can be distinguished at a molecular level from the arrest brought about by other means of growth arrest and does not result from a generalized mechanism which non-specifically shuts down the expression of growth-associated genes. Expand
Terminal differentiation of human promyelocytic leukemia cells induced by dimethyl sulfoxide and other polar compounds.
TLDR
The marked similarity in behavior of HL-60 cells and Friend cells in the presence of these inducing agents suggests that similar molecular mechanisms are involved in the induction of differentiation of these human myeloid and murine erythroid leukemic cells. Expand
Orally active esters of cephalosporin antibiotics. Synthesis and biological properties of acyloxymethyl esters of 7-(D-2-amino-2-phenylacetamido)-3-[5-methyl-(1,3,4-thiadiazol-2-yl)thiomethyl]-3-cephem-4-carboxylic acid.
The synthesis of the acetoxymethyl (AOM), pivaloloxymethyl (POM), and phthalidyl (PHTH) esters ofExpand
5-Fluorouracil derivatives. IV. Synthesis of antitumor-active acyloxyalkyl-5-fluorouracils.
Synthese de fluoro-5 uraciles substitues acyloxy-1' alkyl en 1 et/ou 3 par acylation du fluoro-5 uracile par des alcanoates de chloromethyle ou par reaction de bis-trimethylsiloxy-2,4 fluoro-5Expand
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