Novel N-(3-carboxyl-9-benzyl-β-carboline-1-yl)ethylamino acids: Synthesis, anti-tumor evaluation, intercalating determination, 3D QSAR analysis and docking investigation

Wu, Jianhui; Zhao, Ming; Qian, Keduo; Lee, Kuo‐Hsiung; Morris‐Natschke, Susan L.; Peng, Shiqi

doi:10.1016/j.ejmech.2009.05.006

Cited by 93 publications

(33 citation statements)

References 35 publications

(33 reference statements)

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“…It is shown that the DOCK scores of Trp-Trp-AA-OBzls are 31e62, and ten of them are 51e62. While our previous work indicated that the DOCK scores of the intercalators with high in vivo anti-tumor activity were 50e60 [8,10]. This means that at least ten Trp-Trp-AA-OBzls possibly have high in vivo anti-tumor activity.…”

Section: Resultsmentioning

confidence: 95%

“…It is well documented that Trp-Trp is biologically important either as a dipeptide or as a fragment of some peptides [8,10]. For instance, via a similar ring-opening modification both the antitumor active b-carboline-3-carboxyltryptophan benzyl ester and N-trytophanyl-b-carboline-3-carboxylic acid benzyl ester forms Trp-Trp-OBzl (Fig.…”

Section: Introductionmentioning

confidence: 99%

“…These requirements were generally met in the design of N-(3-carboxyl-9-benzylcarboline-1-yl) ethylamino acids. The docking studies demonstrated that their in vitro antiproliferation and in vivo anti-tumor activities could be predicted with the DOCK scores [8].…”

Section: Introductionmentioning

confidence: 99%

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A class of Trp-Trp-AA-OBzl: Synthesis, in vitro anti-proliferation/in vivo anti-tumor evaluation, intercalation-mechanism investigation and 3D QSAR analysis

Zhang

Yang

Zhao

et al. 2011

European Journal of Medicinal Chemistry

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Section: Resultsmentioning

confidence: 95%

Section: Introductionmentioning

confidence: 99%

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A class of Trp-Trp-AA-OBzl: Synthesis, in vitro anti-proliferation/in vivo anti-tumor evaluation, intercalation-mechanism investigation and 3D QSAR analysis

Zhang

Yang

Zhao

et al. 2011

European Journal of Medicinal Chemistry

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“…Among these action mechanisms intercalation has particular importance in the clinical oncology (Song et al, 2004;Hurley, 2002). Discovering of b-carboline intercalators and exploring their anti-tumor mechanism via physical and chemical approaches have attracted a lot of interests (Wu et al, 2007(Wu et al, , 2009Guan et al, 2006a, b;Eick et al, 2008;Boursereaua and Coldham, 2004). However, the spectra based measurements are usually correlated with the in vitro anti-proliferation activity of b-carboline intercalators (Guan et al, 2006a, b;Cao et al, 2005;Lemster et al, 2009).…”

Section: Introductionmentioning

confidence: 99%

N-[2(3-Carboxyl-9-benzyl-carboline-1-yl)ethyl-1-yl]-amino acids: correlation of spectral property with in vivo anti-tumor activity

Wei

Zhao

et al. 2010

Med Chem Res

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To clarify the relationships of the commonly used spectral measurements and the in vivo activity of b-carboline intercalators N-[2(3-carboxyl-9-benzyl-carboline-1-yl)ethyl-1-yl]-aspartic acid (3a), -tyrosine (3b), -serine (3c), and -threonine (3d) were prepared as the model compounds by using a three-step procedure. In UV measurements of calf thymus DNA (CT DNA) the in vivo active 3a-c induced both hypochromic effect and hypsochromic shift, while the in vivo inactive 3d did not. In CD measurements the in vivo active 3a-c changed the intensities of both positive and negative bands of CT DNA in same direction, while the in vivo inactive 3d induced an opposite change. In fluorescence measurements due to adding CT DNA the increase of the fluorescence intensities of 3a-c were 10-31% higher than that of 3d, and the bathochromic shifts of 3a-c were 2-6 nm higher than that of 3d. The viscositic experiments revealed that 3d possessed the lowest binding ratio. The melting curves indicate that the effect of 3a-c (DT m , 10.8-12.9°C) on the T m of CT DNA was significantly higher than that of 3d (DT m , 4.9°C). Spectroscopic, viscositic, and melting curve investigations are not only able to provide multiple evidences for DNA intercalation mechanism, but also are able to distinguish the in vivo active and inactive N-[2(3-carboxyl-9-benzyl-carboline-1-yl)-ethyl-1-yl]-amino acids.

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“…1), have been reported to display antitumor activities through multiple mechanisms such as intercalating into DNA or inhibiting Topoisomerase I and II, cyclin-dependent kinases (CDK), PLK, or MAO23456. According to the SARs summarized from the reported β-carboline derivatives, the modification on positions-1 or -3 of the parent nucleus would make great influence on their antitumor activities6789.…”

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confidence: 99%

Design, synthesis and biological evaluation of hybrids of β-carboline and salicylic acid as potential anticancer and apoptosis inducing agents

Chen

Jiao

et al. 2016

Sci Rep

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A novel series of hybrids (7a-l, 8a-l) from β-carboline and salicylic acid (SA) were designed and synthesized, and their in vitro biological activities were evaluated. Most of the hybrids displayed potent antiproliferative activity against five cancer cell lines in vitro, showing potencies superior to 5-FU and harmine. In particular, compound 8h selectively inhibited proliferation of liver cancer SMMC-7721 cells but not normal liver LO2 cells, and displayed greater inhibitory selectivity than intermediate 5h and SA. 8h also induced cancer cell apoptosis in an Annexin V-FITC/propidium iodide flow cytometry assay, and triggered the mitochondrial/caspase apoptosis by decreasing mitochondrial membrane potential which was associated with up-regulation of Bax, down-regulation of Bcl-2 and activation levels of the caspase cascade in a concentration-dependent manner. Our findings suggest that the β-carboline/SA hybrids may hold greater promise as therapeutic agents for the intervention of human cancers.

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Novel N-(3-carboxyl-9-benzyl-β-carboline-1-yl)ethylamino acids: Synthesis, anti-tumor evaluation, intercalating determination, 3D QSAR analysis and docking investigation

Cited by 93 publications

References 35 publications

A class of Trp-Trp-AA-OBzl: Synthesis, in vitro anti-proliferation/in vivo anti-tumor evaluation, intercalation-mechanism investigation and 3D QSAR analysis

A class of Trp-Trp-AA-OBzl: Synthesis, in vitro anti-proliferation/in vivo anti-tumor evaluation, intercalation-mechanism investigation and 3D QSAR analysis

N-[2(3-Carboxyl-9-benzyl-carboline-1-yl)ethyl-1-yl]-amino acids: correlation of spectral property with in vivo anti-tumor activity

Design, synthesis and biological evaluation of hybrids of β-carboline and salicylic acid as potential anticancer and apoptosis inducing agents

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