Synthesis and biological evaluation of novel ligustrazine-chalcone derivatives as potential anti-triple negative breast cancer agents

Luo, Yingqi; Wu, Wenhao; Zha, Dailong; Zhou, Wenmin; Wang, Chengxu; Huang, Jianan; Chen, Shaobin; Yu, Lei; Li, Yuanzhi; Huang, Qinghui; Zhang, Jianye; Zhang, Chao

doi:10.1016/j.bmcl.2021.128230

Cited by 19 publications

(8 citation statements)

References 23 publications

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“…Another investigation using human non-small-cell lung cancer found that cardamonin treatment resulted in a reduction in Ki67 expression, and another study found that Ki67 was decreased in murine B16 melanoma cells in C57/BL6 mice upon treatment by xanthohumol chalcone. Chalcone also decreased the Ki67 in an in vivo model of triple-negative breast cancer cells (Luo et al 2021 ).…”

Section: Discussionmentioning

confidence: 98%

[1,2,4] Triazolo [3,4-a]isoquinoline chalcone derivative exhibits anticancer activity via induction of oxidative stress, DNA damage, and apoptosis in Ehrlich solid carcinoma-bearing mice

WalyEldeen

El-Shorbagy

Hassaneen

et al. 2022

Naunyn-Schmiedeberg's Arch Pharmacol

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Despite the advances made in cancer therapeutics, their adverse effects remain a major concern, putting safer therapeutic options in high demand. Since chalcones, a group of flavonoids and isoflavonoids, act as promising anticancer agents, we aimed to evaluate the in vivo anticancer activity of a synthetic isoquinoline chalcone (CHE) in a mice model with Ehrlich solid carcinoma. Our in vivo pilot experiments revealed that the maximum tolerated body weight-adjusted CHE dose was 428 mg/kg. Female BALB/c mice were inoculated with Ehrlich ascites carcinoma cells and randomly assigned to three different CHE doses administered intraperitoneally (IP; 107, 214, and 321 mg/kg) twice a week for two consecutive weeks. A group injected with doxorubicin (DOX; 4 mg/kg IP) was used as a positive control. We found that in CHE-treated groups: (1) tumor weight was significantly decreased; (2) the total antioxidant concentration was substantially depleted in tumor tissues, resulting in elevated oxidative stress and DNA damage evidenced through DNA fragmentation and comet assays; (3) pro-apoptotic genes p53 and Bax, assessed via qPCR, were significantly upregulated. Interestingly, CHE treatment reduced immunohistochemical staining of the proliferative marker ki67, whereas BAX was increased. Notably, histopathological examination indicated that unlike DOX, CHE treatment had minimal toxicity on the liver and kidney. In conclusion, CHE exerts antitumor activity via induction of oxidative stress and DNA damage that lead to apoptosis, making CHE a promising candidate for solid tumor therapy.

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Section: Discussionmentioning

confidence: 98%

[1,2,4] Triazolo [3,4-a]isoquinoline chalcone derivative exhibits anticancer activity via induction of oxidative stress, DNA damage, and apoptosis in Ehrlich solid carcinoma-bearing mice

WalyEldeen

El-Shorbagy

Hassaneen

et al. 2022

Naunyn-Schmiedeberg's Arch Pharmacol

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“…They found that a compound with 4-methoxy substitution on the right aromatic ring has a high activity on MCF-7, HepG2, and HCT1 16 cancer lines, with IC 50 values of 3.44  0.19, 4.64  0.23, and 6.31  0.27 μM, respectively. Luo et al [8] synthesized a series of novel ligustrazine-chalcone hydrides and evaluated in vitro and in vivo antitumor activities. It showed that these compounds exhibited significant in vitro cytotoxicity against MDA-MB-231, MCF-7, A549, and HepG2 cell lines with IC 50 values as low as sub-micromole.…”

Section: ■ Introductionmentioning

confidence: 99%

Synthesis and Cytotoxic Test of Halogen-Substituted Chalcone Against MCF-7 Breast Cancer Cells

Brahmana

Kaban²,

Haro³

et al. 2022

Indones. J. Chem.

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A series of chalcones was synthesized to be (E)-1-(4-chlorophenyl)-3-p-tolyprop-2-en-1-on (1), (E)-1-(4-chlorophenyl)-3-(4-tolyprophenyl) prop-2-en-1-on (2), (E)-1-(3-bromophenyl)-3-p-tolylprop-2-en-1-on (3), and (E)-1-(3-bromophenyl)-3-(4-isopropyl phenyl) prop-2-en-1-on (4) using irradiate microwave method with reaction time from 3, 6, and 8 min at 800 °C and 700 W. The compounds were characterized using TLC, UV-Vis, FTIR, 1H-NMR, and evaluated MCF-7 cancer cell cytotoxic test with Presto BlueTM. All compounds produced were in the form of yellow crystals. The results showed that compounds 2, 3, and 4 were potentially a Como prevention agent and inhibit cell proliferation with IC50 values of 37.24, 422.22, and 22.41 ppm, respectively. While compound 1 had IC50 1,484.75 and no cytotoxic effect. Further tests should be carried out for compounds 2, 3, and 4 against normal cells to measure the compound's safety for normal cells.

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“…TMP is a natural alkaloid monomer pyrazine derivative extracted and isolated from the roots of Ligusticum Chuanxiong Hort, which has been shown to be a potential antitumor agent ( Xie et al, 2019 ). TMP has demonstrated multiple antitumor effects, including inhibiting proliferation ( Luo et al, 2021 ), apoptosis, invasion, and metastasis of malignant tumors ( Bian et al, 2021 ). The introduction of substitutions into the TMP nucleus may improve the antitumor effect ( Xu et al, 2017a ; Wang et al, 2019 ).…”

Section: Introductionmentioning

confidence: 99%

“…A TMP dimer with an alkyl chain as the linker had significantly stronger antitumor activity than the TMP monomer ( Li et al, 2014 ). TMP-chalcone hybrids demonstrated antiproliferative activity in an in vivo model of TNBC ( Luo et al, 2021 ).…”

Section: Introductionmentioning

confidence: 99%

Synthesis and Discovery of Ligustrazine–Heterocycle Derivatives as Antitumor Agents

Zhang

Hou

et al. 2022

Front. Chem.

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Ligustrazine (TMP) is a natural pyrazine alkaloid extracted from the roots of Ligusticum Chuanxiong Hort, which has the potential as an antitumor agent. A series of 33 ligustrazine–heterocycle (TMPH) derivatives were designed, synthesized, and investigated via antitumor screening assays, molecular docking analysis, and prediction of drug-like properties. TMP was attached to other heterocyclic derivatives by an 8–12 methylene alkyl chain as a linker to obtain 33 TMPH derivatives. The structures were confirmed by 1H-NMR, 13C-NMR, and high-resolution mass spectroscopy spectral (HR-MS) data. The antiproliferative activity against human breast cancer MCF-7, MDA-MB-231, mouse breast cancer 4T1, mouse fibroblast L929, and human umbilical vein endothelial HUVEC cell lines was evaluated by MTT assay. Compound 12–9 displayed significant inhibitory activity with IC50 values in the low micromolar range (0.84 ± 0.02 µM against the MDA-MB-231 cell line). The antitumor effects of compound 12–9 were further evaluated by plate cloning, Hoechst 33 342 staining, and annexin V-FITC/PI staining. The results indicated that compound 12–9 inhibited the proliferation and apoptosis of breast cancer cells. Furthermore, molecular docking of compound 12–9 into the active site of the Bcl-2, CASP-3, and PSMB5 target proteins was performed to explore the probable binding mode. The 33 newly synthesized compounds were predicted to have good drug-like properties in a theoretical study. Overall, these results indicated that compound 12–9 inhibited cell proliferation through PSMB5 and apoptosis through Bcl-2/CASP-3 apoptotic signaling pathways and had good drug-like properties. These results provided more information, and key precursor lead derivatives, in the search for effective bioactive components from Chinese natural medicines.

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Synthesis and biological evaluation of novel ligustrazine-chalcone derivatives as potential anti-triple negative breast cancer agents

Cited by 19 publications

References 23 publications

[1,2,4] Triazolo [3,4-a]isoquinoline chalcone derivative exhibits anticancer activity via induction of oxidative stress, DNA damage, and apoptosis in Ehrlich solid carcinoma-bearing mice

[1,2,4] Triazolo [3,4-a]isoquinoline chalcone derivative exhibits anticancer activity via induction of oxidative stress, DNA damage, and apoptosis in Ehrlich solid carcinoma-bearing mice

Synthesis and Cytotoxic Test of Halogen-Substituted Chalcone Against MCF-7 Breast Cancer Cells

Synthesis and Discovery of Ligustrazine–Heterocycle Derivatives as Antitumor Agents

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