Boron analogues of amino acids VI. Synthesis and characterization of di- and tripeptide analogues as antineoplastic, anti-inflammatory and hypolipidemic agents

Sood, Anup; Sood, CK; Spielvogel, Bernard F.; Hall, I. H.

doi:10.1016/0223-5234(90)90113-h

Cited by 45 publications

(21 citation statements)

References 14 publications

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“…Di-and tripeptides with Me 3 NBH 2 CO 2 H or H 3 NBH 2 CO 2 H at the N-terminus were synthesized by Spielvogel et al [26]. In general, these peptides showed weaker antineoplastic activity than the previously discussed α-amino acid analogues.…”

Section: Metal Complexes Di-and Tripeptidesmentioning

confidence: 99%

Synthesis and Pharmacological Activities of Amine-Boranes

Burnham¹

2005

CMC

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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.

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Section: Metal Complexes Di-and Tripeptidesmentioning

confidence: 99%

Synthesis and Pharmacological Activities of Amine-Boranes

Burnham¹

2005

CMC

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“…The general synthetic sequence is based on the asymmetric methodology developed by Matteson [40]. In order to introduce the amino group in the a-position of boron atom, hexamethyldisilazane (HMDS) was used to displace the chloride in compound (102) of (117), and (118) were obtained using benzyl-chloroformate and a mixture of AcOH and Ac 2 O, respectively. [83].…”

Section: Synthesis Of Arginine A-aminoboronic Acidsmentioning

confidence: 99%

“…This resemblance has inspired extensive biological screening of these molecules, and the promising early results led to the syntheses of a large number of ester [96][97][98][99], amide [100,101], peptide [102,103], hydroxamic acid [104], and transition metal [105][106][107] derivatives of amine-carboxyboranes (A-BH 2 COX, X ¼ OR, NR 1 R 2 , or NHOH) containing a broad range substitutes, among other amine-boranes, which have been reviewed recently [2,108,109].…”

Section: Synthesis and Activity Of Amine-carboxyboranes And Their Dermentioning

confidence: 99%

Chemistry of α‐Aminoboronic Acids and their Derivatives

Dembitsky

Srebnik

2009

Amino Acids, Peptides and Proteins in Organic Chemistry

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“…Previously we have examined a number of amine-cyanoboranes [l] aminecarboxyboranes and their amides and esters [2][3][4][5], di-and triopeptide boranes [6], heterocyclic-amine boranes [7], polyborate salts [8], choline and thiocholine boranes [9], phosphoacetate boranes[10] and deoxyribonucleoside cyanoboranes [ll]. These agents were effective in rodents at 8 mg/kg/day, significantly lowering both serum cholesterol and triglyceride levels after 14-16 days.…”

Section: Introductionmentioning

confidence: 99%

Hypolipidemic Activity of Amine‐Borane Aducts of Cyclohexylamineand Toluidine in Rodents

Burnham

Chen

Sood³

et al. 1995

Metal-Based Drugs

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The amine-borane adducts of cyclohexylamine and toluidine were observed to be potent hypolipidemic agents in mice, I.P. and rats orally at 8 mg/kg/day lowering both serum cholesterol and triglyceride levels after 14-16 days. These compounds were able to lower tissue lipids including the cholesterol content of the aorta wall. The agents successfully lower VLDL-and LDLocholesterol content while elevating HDL-cholesterol content significantly. The agents also modulate lipid regulatory enzyme activities in a manner to reduce liver lipid levels. These studies demonstrate that the nitrogen atom does not have to be apart of the aromatic ring as in heterocyclic-amine borane to afford good hypolipidemic activity in rodents.

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Boron analogues of amino acids VI. Synthesis and characterization of di- and tripeptide analogues as antineoplastic, anti-inflammatory and hypolipidemic agents

Cited by 45 publications

References 14 publications

Synthesis and Pharmacological Activities of Amine-Boranes

Synthesis and Pharmacological Activities of Amine-Boranes

Chemistry of α‐Aminoboronic Acids and their Derivatives

Hypolipidemic Activity of Amine‐Borane Aducts of Cyclohexylamineand Toluidine in Rodents

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