Design, synthesis and in vitro and in vivo antitumor activities of novel bivalent β-carbolines

Shi, Buxi; Cao, Rihui; Fan, Wenhong; Guo, Liang; Ma, Qin; Chen, Xuemei; Zhang, Guoxian; Qiu, Liqin; Song, Huacan

doi:10.1016/j.ejmech.2012.11.033

Cited by 53 publications

(20 citation statements)

References 40 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In this study, we were interested in using evodiamine as a lead compound to develop anticancer drug candidates, because of its: (1) known broad-spectrum antitumor activities; (2) significant difference of toxicity between cancer cells and normal peripheral blood mononuclear cells; (3) good drug-like molecule features as judged by both the criteria of Lipinski's "rule of five" and the "verb rule"; (4) good synthetic accessibility for its diversity of derivatives. In our continuous search for novel improved antitumor agents [24][25][26][27][28][29], we report herein the design, synthesis and testing of novel N13-substituted evodiamine derivatives as antitumor agents.…”

Section: Introductionmentioning

confidence: 99%

Design, Synthesis and Evaluation of N13-Substituted Evodiamine Derivatives against Human Cancer Cell Lines

Song

Chen

et al. 2013

Molecules

Self Cite

View full text Add to dashboard Cite

Abstract:Attempting to improve the anticancer activity and solubility of evodiamine in simulated gastric fluid (SGF) and simulated intestinal fluid (SIF) solutions, thirty-eight N13-substituted evodiamine derivatives were designed, synthesized and tested for antitumor activities against six kinds of human cancer cell lines, namely prostate cancer (DU-145 and PC-3), lung cancer (H460), breast cancer (MCF-7), colon cancer (HCT-5) and glioblastoma (SF-268). The solubility of these compounds in SGF and SIF solutions was evaluated, and apoptosis induced by 2-2, 2-3, 2-16 and 3-2 was determined. The results showed: (1) among all compounds examined, 2-16 showed the highest antitumor activity and a broader spectrum of activity, with IC 50 values ranging from 1-2 µM; (2) their solubility was obviously improved; (3) 2-3, 2-16 and 3-2 had a significant impact inducing apoptosis in some cancer cell lines. The preliminary structure-activity relationships of these derivatives were discussed.

show abstract

Section: Introductionmentioning

confidence: 99%

Design, Synthesis and Evaluation of N13-Substituted Evodiamine Derivatives against Human Cancer Cell Lines

Song

Chen

et al. 2013

Molecules

Self Cite

View full text Add to dashboard Cite

show abstract

“…The N 9 substituted β -carboline-3-carboxylic acid methyl esters ( 4A , 4B , 4C , and 4D ) prepared in the above steps were hydrolyzed and reacted with dibromoalkane to obtain a series of bivalent β -carboline-3-carboxylic acid derivatives ( 6a-6f , 6g-6l , 6m-6r , and 6s-6x ), as previously described [ 34 , 35 , 37 , 48 ]. Reaction routes and conditions are shown in Scheme 2 .…”

Section: Methodsmentioning

confidence: 99%

“…Bivalent β -carbolines linked at the C 6 position or N 9 position have been synthesized, and were found to be potential anti-Alzheimer agents [ 33 ]. In addition, the synthesis and evaluation of bivalent β -carbolines linked by 3–10 methylene units at the N 9 position as antitumor agents have also been reported [ 34 ]. Our group has synthesized 25 bivalent β -carbolines modified at the C 1 (-CH 3 ), C 7 (-OCH 3 ), and N 9 positions (-CH 3 and -CH 2 Ph 2 ), and dimerized at the C 2 position, and the results showed that the dimerization could significantly increase antitumor activity of β -carbolines.…”

Section: Introductionmentioning

confidence: 99%

Synthesis and In Vitro Antitumor Activity of Novel Bivalent β-Carboline-3-carboxylic Acid Derivatives with DNA as a Potential Target

Dai

et al. 2018

IJMS

View full text Add to dashboard Cite

A series of novel bivalent β-carboline derivatives were designed and synthesized, and in vitro cytotoxicity, cell apoptosis, and DNA-binding affinity were evaluated. The cytotoxic results demonstrated that most bivalent β-carboline derivatives exhibited stronger cytotoxicity than the corresponding monomer against the five selected tumor cell lines (A549, SGC-7901, Hela, SMMC-7721, and MCF-7), indicating that the dimerization at the C3 position could enhance the antitumor activity of β-carbolines. Among the derivatives tested, 4B, 6i, 4D, and 6u displayed considerable cytotoxicity against A549 cell line. Furthermore, 4B, 6i, 4D, and 6u induced cell apoptosis in a dose-dependent manner, and caused cell cycle arrest at the S and G2/M phases. Moreover, the levels of cytochrome C in mitochondria, and the expressions of bcl-2 protein, decreased after treatment with β-carbolines, which indicated that 6i and 6u could induce mitochondria-mediated apoptosis. In addition, the results of UV-visible spectral, thermal denaturation, and molecular docking studies revealed that 4B, 6i, 4D, and 6u could bind to DNA mainly by intercalation.

show abstract

“…The experimental details are shown in supporting information (Appendix S1). Antitumor assay in vivo Antitumor activity against mice bearing H22 liver cancer and B16 melanoma was performed as described by Cao et al with a slight modification (18). The experimental details are shown in supporting information (Appendix S1).…”

Section: In Vitro Evaluation Of Antiproliferative Activitymentioning

confidence: 99%

Synthesis and Biological Evaluation of Oxygen‐containing Heterocyclic Ring‐fused 23‐Hydroxybetulinic Acid Derivatives as Antitumor Agents

Zhang

Zhu

et al. 2015

Chem Biol Drug Des

View full text Add to dashboard Cite

A collection of isoxazole and oxadiazole substituted 23-hydroxybetulinic acid (HBA) derivatives were designed, synthesized and evaluated for their antitumor activity. Most of the newly synthesized compounds exhibited more potent antiproliferative activity than patent compound 23-hydroxybetulinic acid, especially 13e and 14a were about four- to sevenfold more potent against all tested cancer cell lines than 23-hydroxybetulinic acid. Furthermore, the in vivo antitumor activity of 13e and 14a was validated in H22 liver cancer and B16 melanoma xenograft mouse models. The structure-activity relationships of these 23-hydroxybetulinic acid derivatives were also discussed based on the present investigation.

show abstract

Design, synthesis and in vitro and in vivo antitumor activities of novel bivalent β-carbolines

Cited by 53 publications

References 40 publications

Design, Synthesis and Evaluation of N13-Substituted Evodiamine Derivatives against Human Cancer Cell Lines

Design, Synthesis and Evaluation of N13-Substituted Evodiamine Derivatives against Human Cancer Cell Lines

Synthesis and In Vitro Antitumor Activity of Novel Bivalent β-Carboline-3-carboxylic Acid Derivatives with DNA as a Potential Target

Synthesis and Biological Evaluation of Oxygen‐containing Heterocyclic Ring‐fused 23‐Hydroxybetulinic Acid Derivatives as Antitumor Agents

Contact Info

Product

Resources

About