Antineoplastic Activity of a Series of Boron Analogues of α-Amino Acids

Hall, Iris H.; Gilbert, Colleen; McPhail, Andrew T.; Morse, Karen W.; Hassett, Karen L.; Spielvogel, Bernard F.

doi:10.1002/jps.2600740712

Cited by 41 publications

(25 citation statements)

References 12 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Acute toxicity studies showed a decrease in hematocrit values after drug treatment. Marginal myocardial damage and changes in kidney and liver morphologies were observed [17,23].…”

Section: Trimethylamine-carboxyboranementioning

confidence: 96%

See 1 more Smart Citation

Synthesis and Pharmacological Activities of Amine-Boranes

Burnham¹

2005

CMC

View full text Add to dashboard Cite

A number of amine-boranes and related derivatives possess a wide range of biological activities including antineoplastic, antiviral, hypolipidemic, anti-inflammatory activities, anti-osteoporotic and dopamine receptor antagonist activities. The compounds include borane complexes of alpha-amino acids, aromatic, aliphatic and heterocyclic amines, and nucleosides. The syntheses of amine-borane derivatives are generally carried out by first preparing a tertiary amine- or phosphine-cyano- or carboxyborane to serve as a borane donor for a subsequent Lewis acid exchange reaction. Borane adducts of simple aliphatic amines, heterocyclic amines and nucleic acids demonstrated potent cytotoxic activity in vitro and in vivo against murine and human tumor models. These boron-containing compounds were shown to inhibit DNA synthesis; such inhibition was caused primarily by reducing de novo purine biosynthesis via inhibition of PRPP amidotransferase, IMP dehydrogenase and dihydrofolate reductase activities. Aliphatic, heterocyclic and nucleoside amine-boranes have also been shown to possess hypolipidemic activity in mice and rats. Many boron derivatives from different chemical classes demonstrated both cytotoxic and hypolipidemic activities. They decreased low-density lipoprotein (LDL) cholesterol while increasing high-density lipoprotein (HDL) cholesterol levels. The mode of action of these compounds in the 50-100 microM concentration range appeared to be by increasing lipid excretion from the body and by inhibiting rate-limiting enzyme activities for the de novo synthesis of lipids and cholesterol (e.g., phosphatidylate phosphohydrolase, ATP-dependent citrate lyase, cytoplasmic acetyl coenzyme A [CoA] synthetase, HMG CoA reductase, and acetyl CoA carboxylase). Selected amine-boranes (e.g., trimethylamine-cyanoborane, N-methylmorpholine-cyanoborane, and the base-boronated 2'-deoxynucleosides) have anti-inflammatory, analgesic, anti-arthritic and anti-osteoporotic activities.

show abstract

“…Acute toxicity studies showed a decrease in hematocrit values after drug treatment. Marginal myocardial damage and changes in kidney and liver morphologies were observed [17,23].…”

Section: Trimethylamine-carboxyboranementioning

confidence: 96%

“…The activities of the proteolytic enzymes cathepsin D and trypsin were also reduced by these derivatives. The compounds also demonstrated anti-oxidant activity in the Fenton reaction [70]. …”

Section: Base-boronated 2'-deoxynucleosidesmentioning

confidence: 98%

Synthesis and Pharmacological Activities of Amine-Boranes

Burnham¹

2005

CMC

View full text Add to dashboard Cite

show abstract

“…Amine and phosphine cyanoboranes are an intriguing group of compounds that have inspired extensive biological screening. The promising early results led to the synthesis of a large number derivatives, some of which have been shown in model studies to have potent antitumor [10][11][12][13][14][15], anti-inflammatory [16][17][18], hypolipidemic [11,19], anti-hyperlipidemic [20], anti-ostoeoporotic [21], anti-neoplastic [22][23][24], BNCT [25], and other promising biological activities [26,27]. In the present study, the diborane (4) derivatives of the corresponding amine cyanoborane were synthesized as their 2LiBr complexes from of the monobromo derivative of the corresponding amine cyanoborane, followed by B-B coupling using elemental sodium or n-BuLi.…”

Section: Introductionmentioning

confidence: 99%

Diborane (4) derivatives via coupling of amine monobromocyanoboranes: Study of the bromination of amine cyanoborane and molecular structures of the amine dibromocyanoboranes

Takrouri¹,

Shalom²,

Goldberg³

et al. 2005

Journal of Organometallic Chemistry

View full text Add to dashboard Cite

“…[22][23][24][25] Trimethylamine-carboxyborane inhibits rat Walker 256 carcinosarcoma growth and mouse Lewis lung growth, 1 and has been demonstrated to have potent cytotoxicity. 23,24 Further structural modifications have included amidation and esterification of trimethylaminecarboxyboranes, 26 heterocyclic amine-carboxyboranes, 27 di-and tri-peptide carboxyboranes, 28 boronated nucleic acids, 29 metal complexes of trimethylamine-carboxyborane, 15,30 and substituted carboranes and polyhedral hydroborate salts. 31 All of these derivatives were very effective in inhibiting DNA synthesis in L1210 lymphocytic leukemia cells.…”

Section: Introductionmentioning

confidence: 99%

The cytotoxicity of trifluoromethyl boron derivatives and mode of action in human Tmolt3 T leukemic cells

Hall

Henry

Peaty

et al. 2000

Appl. Organometal. Chem.

View full text Add to dashboard Cite

Trifluoromethylboron derivatives proved to be cytotoxic in a number of murine and human leukemic and lymphoma screens. Solid tumor growth, e.g. glioma HS 683, breast Mck‐7 and colon adenocarcinoma SW480, was reduced significantly by the compounds. Human Tmolt3 T‐cell leukemia DNA synthesis was inhibited preferentially by the derivatives, with marginal effects on RNA and protein syntheses, after 60 min at 100 µM. The agents appeared to act by multiple mechanisms in that they inhibited the activities of DNA polymerase α, dihydrofolate reductase and nucleosides, significantly within 60 min at 100 µM. Deoxyribonucleotide pools were reduced after 60 min incubation with the compounds. Tmolt3 DNA fragmentation and reduced ct‐DNA viscosity were evident after 24 h of incubation at 100 µM. ct‐DNA thermal denaturation studies indicated that the agents caused some type of interaction with the bases of DNA. Copyright © 2000 John Wiley & Sons, Ltd.

show abstract

Antineoplastic Activity of a Series of Boron Analogues of α-Amino Acids

Cited by 41 publications

References 12 publications

Synthesis and Pharmacological Activities of Amine-Boranes

Synthesis and Pharmacological Activities of Amine-Boranes

Diborane (4) derivatives via coupling of amine monobromocyanoboranes: Study of the bromination of amine cyanoborane and molecular structures of the amine dibromocyanoboranes

The cytotoxicity of trifluoromethyl boron derivatives and mode of action in human Tmolt3 T leukemic cells

Contact Info

Product

Resources

About