Specific inhibition of cyclin-dependent kinases and cell proliferation by harmine

Song, Yuanlin; Kesuma, Djohan; Wang, Jian; Deng, Yu; Duan, Jin‐Ao; Wang, Jerry H.; Qi, Robert Z.

doi:10.1016/j.bbrc.2004.03.019

Cited by 163 publications

(96 citation statements)

References 24 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Harmine showed inhibitory effects on cell proliferation against all human carcinoma cells [11] . In cytotoxicity assays, harmine exhibited a strong inhibitory effect on the growth and proliferation of carcinoma cells whereas it had no significant effect on quiescent fibroblasts [40] . Evaluation on harmine cytotoxicity toward proliferation and differentiation of HL60 cells, alone or in combination with ATRA and G-CSF, showed that harmine reduced proliferation in a dose and time dependent manner [7] .…”

Section: Effect Of Harmine Against Cancermentioning

confidence: 96%

A review on medicinal importance, pharmacological activity and bioanalytical aspects of beta-carboline alkaloid “Harmine”

Patel

Gadewar

Tripathi

et al. 2012

Asian Pacific Journal of Tropical Biomedicine

213

120

View full text Add to dashboard Cite

Section: Effect Of Harmine Against Cancermentioning

confidence: 96%

A review on medicinal importance, pharmacological activity and bioanalytical aspects of beta-carboline alkaloid “Harmine”

Patel

Gadewar

Tripathi

et al. 2012

Asian Pacific Journal of Tropical Biomedicine

213

120

View full text Add to dashboard Cite

“…Interestingly, harmine was once used as an anti-parkinsonian agent and was soon abandoned for its disappointing effectiveness [6]. Harmine and harmaline showed special affinity to the central nervous system (CNS) and exhibited extensive bioactivities such as multi-enzymes inhibitions including monoamine oxidaze type-A [7,8], cyclin-dependent kinases [9], N-acetyltransferase [10] and Na-K ATPase [11], cytotoxicity and antitumour activities [12,13], anti-bacterial activity [14], antiplasmodial activity [15], antileishmanial activity [16], immunomodulator properties [17], temperature-lowering effect [18], cardiovascular actions [19] and so on. Recent research reported that the alkaloids showed potential inhibitory effects on the acetylcholinesterase (AChE) activity using an in vitro thin-layer chromatography (TLC)-bioautographic assay, and ten alkaloids isolated were evaluated based on their inhibitory ability [20].…”

Section: Introductionmentioning

confidence: 99%

Characterization and determination of trace alkaloids in seeds extracts fromPeganum harmalalinn. Using LC-ESI-MS and HPLC

Liu

Zhao

Cheng

et al. 2013

Acta Chromatographica

View full text Add to dashboard Cite

Summary. Harmaline and harmine accounted for more than 70% in composition in extracts of P. harmala. More attention, however, should be paid to the other alkaloids which would be favorable or unfavorable to the efficacy and safety of the products. It was necessary to determine these trace alkaloids in the extracts; thereafter, most of them have been characterized. Diglycoside vasicine, vasicine, vasicinone, harmalol, harmol, tetrahydroharmine, 8-hydroxy-harmine, ruine, harmaline, and harmine were separated and identified with reference substances and characteristic MS spectra in extracts by liquid chromatography-electrospray ionization-mass spectrometry (LC-ESI-MS) and high-performance liquid chromatography (HPLC). Three trace alkaloids, vasicine, harmalol, and harmol were determined using the developed chromatographic separation method subsequently. The average contents of vasicine, harmalol, and harmol in extracts of ten batches were 2.53 ± 0.73, 0.54 ± 0.19, and 0.077 ± 0.03%, respectively. The total content of the three alkaloids was 3.23 ± 0.90% (from 1.81 to 4.48%). For rough estimation of all the relative alkaloids except of harmaline and harmine, the average total areas of all peaks in extracts varied from 4.35 to 26.64% detected at 220, 254, 265, 280, and 380 nm, respectively. The results indicated that area normalization method was powerless for the quality evaluation for traditional herb medicine consisting of numerous compounds with highly differential features. It might be concluded that LC-MS or HPLC could be utilized as a qualitative and quantitative analytical method for quality control of the extracts from seeds of P. harmala L.

show abstract

“…These compounds have been shown to intercalate into DNA, to inhibit CDK, topisomerase and monoamine oxidase, and to interact with benzodiazepine receptors (BZ), 5-hydroxy serotonin receptors (5-HT), dopamine (DA) and imidazoline receptors. [15][16][17][18][19][20][21][22][23] Inspired by these results, our research group recently focused on first of all, using a structure-guided strategy based on CDK2 as appropriate means to generate potent CDK2 inhibitors; then to synthesize disubstituted β-carbolines and to complete their biological evaluation study. As a part of our systematic work, in this paper, structure modification of β-carboline based on increasing its hydrophobic nature has been adopted.…”

mentioning

confidence: 99%

Synthesis and Structure of the β-Carboline Derivatives and Their Binding Intensity with Cyclin-Dependent Kinase 2

Wang

Jin

Lin

et al. 2012

CHEMICAL & PHARMACEUTICAL BULLETIN

View full text Add to dashboard Cite

Series of 3-substituted of 6-aminosulfonyl-β-carbolines were designed and synthesized. In addition, the binding mode of these β-carboline derivatives with cyclin-dependent kinase 2 (CDK2) was studied by means of fluorescence measurements and molecular docking calculation. The results showed that replacement of 3-cyclohexylmethoxy group will increase the hydrophobic binding interaction with the deep hydrophobic pocket of CDK2 correlate to the higher binding intensity.Key words cyclin-dependent kinase 2; β-carboline; synthesis; molecular docking; fluorescence It is well known that the phases of the cell cycle are driven by cyclin-dependent kinases (CDKs). Upon complexation with its activating proteins, cyclin E or cyclin A, cyclin-dependent kinase 2 (CDK2) modulates the activity of many cellular substrates via phosphorylation on serine (Ser) and/or threonine (Thr) residues.1-4) Abnormal CDK control of the cell cycle has been strongly linked to the molecular pathology of cancer. 5)The importance of CDK2 for cell cycle progression has led to an active pursuit of small molecule inhibitors of this enzyme as a possible treatment against cancer and other hyper-proliferative disorders.6-9) All CDK inhibitors, identified so far, function by competing with ATP for binding to the catalytic site. Actually several CDK inhibitors have entered clinical evaluation for the treatment of cancer, including flavopiridol, amino-thiazole compound.10) In our program to develop CDK2 inhibitors, we recently investigate the β-carboline alkaloids containing a planar tricyclic system as a large group of naturally-occurring and synthetic alkaloids, [11][12][13][14] which has a broad spectrum of biochemical effects and pharmaceutical properties. These compounds have been shown to intercalate into DNA, to inhibit CDK, topisomerase and monoamine oxidase, and to interact with benzodiazepine receptors (BZ), 5-hydroxy serotonin receptors (5-HT), dopamine (DA) and imidazoline receptors. [15][16][17][18][19][20][21][22][23] Inspired by these results, our research group recently focused on first of all, using a structure-guided strategy based on CDK2 as appropriate means to generate potent CDK2 inhibitors; then to synthesize disubstituted β-carbolines and to complete their biological evaluation study. As a part of our systematic work, in this paper, structure modification of β-carboline based on increasing its hydrophobic nature has been adopted. Herein we reported the design and synthesis of series of 3-substituted of 6-aminosulfonyl-β-carbolines. Series of 3-substituted compounds with different hydrophobic groups (Chart 1) were synthesized and one of their structures was elucidated with X-ray crystal analysis. The new derivatives were prepared following the reaction sequences depicted in Charts 2-4. Their binding intensity with CDK2 was measured by fluorescence spectroscopy. ExperimentalSynthesis The target compounds were prepared using the reaction sequence. All the chemical structures of the synthesized compounds were confirmed by spectroscopic me...

show abstract

Specific inhibition of cyclin-dependent kinases and cell proliferation by harmine

Cited by 163 publications

References 24 publications

A review on medicinal importance, pharmacological activity and bioanalytical aspects of beta-carboline alkaloid “Harmine”

A review on medicinal importance, pharmacological activity and bioanalytical aspects of beta-carboline alkaloid “Harmine”

Characterization and determination of trace alkaloids in seeds extracts fromPeganum harmalalinn. Using LC-ESI-MS and HPLC

Synthesis and Structure of the β-Carboline Derivatives and Their Binding Intensity with Cyclin-Dependent Kinase 2

Contact Info

Product

Resources

About