Synthesis and Antineoplastic Activity of Some Cyano-, Carboxy-, Carbomethoxy-, and Carbamoylborane Adducts of Heterocyclic Amines

Sood, Cynthia K.; Sood, Anup; Spielvogel, Bernard F.; Yousef, Jihan A.; Burnham, Bruce S.; Hall, Iris H.

doi:10.1002/jps.2600801209

Cited by 36 publications

(27 citation statements)

References 33 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The most common borane functionalities present in the pharmacologically active compounds are borane (BH 3 ), cyanoborane (BH 2 CN), carboxyborane (BH 2 1) and (2)]: 1) by refluxing the amine hydrochloride and sodium cyanoborohydride in tetrahydrofuran (THF) [8] or 2) via a Lewis acid exchange reaction, either by using equimolar or excess amounts of a cyanoborane and the amine refluxed in THF or dimethylformamide (DMF) or by using excess amine, carrying out the reaction neat at 60-70°C [9]. In the Lewis acid exchange reaction, a weakly basic or bulky amine or phosphine, as its substituted borane adduct, is exchanged for a more basic or less bulky amine.…”

Section: Synthesismentioning

confidence: 99%

Synthesis and Pharmacological Activities of Amine-Boranes

Burnham¹

2005

CMC

Self Cite

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

Section: Synthesismentioning

confidence: 99%

Synthesis and Pharmacological Activities of Amine-Boranes

Burnham¹

2005

CMC

Self Cite

View full text Add to dashboard Cite

show abstract

“…[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

“…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%