Combination of amino acid/dipeptide with ligustrazine-betulinic acid as antitumor agents

Xu, Bing; Yan, Wenqiang; Xu, Xin; Wu, Gaorong; Zhang, Chenze; Han, Yaotian; Chu, Fuxiang; Zhao, Rui; Wang, Peng-Long; Lei, Haimin

doi:10.1016/j.ejmech.2017.02.036

Cited by 28 publications

(25 citation statements)

References 37 publications

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“…The advantage of BA‐conjugated compounds in inducing a higher cytotoxic activity involving apoptosis associated with loss of mitochondrial membrane potential and increase in intracellular free Ca 2+ have been reported in eukaryotic cells (Xu et al . ). Thus, these minor compounds could be acting as a BA carrier into the plasma membrane, and then potentiating this effect.…”

Section: Resultsmentioning

confidence: 97%

“…The marked action of DCMF when compared with BA is possibly due to its lipophilic characteristics, where other compounds might act as a coadjuvant probably forming BA-conjugates in order to better interact with the cell membrane (Costa et al 2017). The advantage of BA-conjugated compounds in inducing a higher cytotoxic activity involving apoptosis associated with loss of mitochondrial membrane potential and increase in intracellular free Ca 2+ have been reported in eukaryotic cells (Xu et al 2017). Thus, these minor compounds could be acting as a BA carrier into the plasma membrane, and then potentiating this effect.…”

Section: Resultsmentioning

confidence: 99%

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Antimicrobial activity of Mimosa caesalpiniifolia Benth and its interaction with antibiotics against Staphylococcus aureus strains overexpressing efflux pump genes

Silva

Monção

Araújo

et al. 2019

Lett Appl Microbiol

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This study aimed to evaluate the antimicrobial activity of the dichloromethane fraction (DCMF) from the stem bark of Mimosa caesalpiniifolia and its effect on the activity of conventional antibiotics against Staphylococcus aureus strains overexpressing specific efflux pump genes. DCMF showed activity against S. aureus, Staphylococcus epidermidis and Candida albicans. Addition of DCMF at subinhibitory concentrations to the growth media enhanced the activity of norfloxacin, ciprofloxacin and ethidium bromide against S. aureus strains overexpressing norA suggesting the presence of efflux pump inhibitors in its composition. Similar results were verified for tetracycline against S. aureus overexpressing tetK, as well as, for ethidium bromide against S. aureus overexpressing qacC. These results indicate that M. caesalpiniifolia is a source of molecules able to modulate the fluoroquinolone‐ and tetracycline‐resistance in S. aureus probably by inhibition of NorA, TetK and QacC respectively. Significance and Impact of the Study Drug resistance is a common problem in patients with infectious diseases. Dichloromethane fraction from the stem bark of Mimosa caesalpiniifolia showed antimicrobial activity against Gram‐positive bacterium Staphylococcus aureus and against Candida albicans, but did not show activity against Gram‐negative specie Escherichia coli. Moreover, this fraction was able to potentiate the action of norfloxacin, ciprofloxacin and tetracycline against S. aureus strains overexpressing different efflux pump genes. Thus, Mimosa caesalpiniifolia is a source of efflux pump inhibitors which could be used in combination with fluoroquinolones or tetracycline in the treatment of infectious diseases caused by S. aureus strains overexpressing efflux pump genes.

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Section: Resultsmentioning

confidence: 97%

Section: Resultsmentioning

confidence: 99%

Antimicrobial activity of Mimosa caesalpiniifolia Benth and its interaction with antibiotics against Staphylococcus aureus strains overexpressing efflux pump genes

Silva

Monção

Araújo

et al. 2019

Lett Appl Microbiol

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“…In this context, several studies reported the development of different ligustrazine-based hybrids such as ligustrazine-curcumin hybrids, 17,18 ligustrazine-terpenes hybrids 19 and others. 20,21 The aforementioned findings have inspired and guided us to design and synthesize a new set of HDAC inhibitors (7a-c and 8a,b) utilizing ligustrazine as a novel cap moiety, and achieving the pharmacophoric features required to induce the desired inhibition ( Figure 1). The newly synthesized ligustrazine-based derivatives (7a-c and 8a,b) were evaluated for their potential inhibitory activity toward two class I histone deacetylases, namely HDAC1 and HDAC2.…”

Section: Introductionmentioning

confidence: 99%

<p>Design, Synthesis and Biological Evaluation of New HDAC1 and HDAC2 Inhibitors Endowed with Ligustrazine as a Novel Cap Moiety</p>

Al-Sanea

Gotina

Mohamed

et al. 2020

DDDT

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Introduction: Histone deacetylases (HDACs) represent one of the most validated cancer targets. The inhibition of HDACs has been proven to be a successful strategy for the development of novel anticancer candidates. Methods: This work describes design and synthesis of a new set of HDAC inhibitors (7a-c and 8a, b) utilizing ligustrazine as a novel cap moiety, and achieving the pharmacophoric features required to induce the desired inhibition. Results: The newly synthesized derivatives were evaluated for their potential inhibitory activity toward two class I histone deacetylases, namely HDAC1 and HDAC2. The tested ligustrazine-based compounds were more potent toward HDAC2 (IC 50 range: 53.7-205.4 nM) than HDAC1 (IC 50 range: 114.3-2434.7 nM). Furthermore, the antiproliferative activities against two HDAC-expressing cancer cell lines; HT-29 and SH-SY5Y were examined by the MTT assay. Moreover, a molecular docking study of the designed HDAC inhibitors (7a-c and 8a,b) was carried out to investigate their binding pattern within their prospective targets; HDAC1 (PDB-ID: 4BKX) and HDAC2 (PDB-ID: 6G3O). Discussion: Compound 7a was found to be the most potent analog in this study toward HDAC1 and HDAC2 with IC 50 values equal 114.3 and 53.7 nM, respectively. Moreover, it was the most effective counterpart (IC 50 = 1.60 µM), with 4.7-fold enhanced efficiency than reference drug Gefitinib (IC 50 = 7.63 µM) against SH-SY5Y cells. Whereas, compound 8a (IC 50 = 1.96 µM) was the most active member toward HT-29 cells, being 2.5-times more potent than Gefitinib (IC 50 = 4.99 µM). Collectively, these results suggest that 7a merits further optimization and development as an effective new HDACI lead compound.

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“…Methionine anthraquinone derivatives were found to have lower activity compared to MX-amino acids derivatives, while lysine anthraquinone derivatives had the highest activity. Xu et al then combined ligustrazine-birch acid with amino acids and dipeptides, which raised its antitumor activity compared to unmodified ligustrazine-betulinic acid [16].…”

Section: Introductionmentioning

confidence: 99%

Novel Anthraquinone Compounds Inhibit Colon Cancer Cell Proliferation via the Reactive Oxygen Species/JNK Pathway

Guo

Guan

et al. 2020

Molecules

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A series of amide anthraquinone derivatives, an important component of some traditional Chinese medicines, were structurally modified and the resulting antitumor activities were evaluated. The compounds showed potent anti-proliferative activities against eight human cancer cell lines, with no noticeable cytotoxicity towards normal cells. Among the candidate compounds, 1-nitro-2-acyl anthraquinone-leucine (8a) showed the greatest inhibition of HCT116 cell activity with an IC50 of 17.80 μg/mL. In addition, a correlation model was established in a three-dimensional quantitative structure-activity relationship (3D-QSAR) study using Comparative Molecular Field Analysis (CoMFA) and comparative molecular similarity index analysis (CoMSIA). Moreover, compound 8a effectively killed tumor cells by reactive oxygen species (ROS)-JNK activation, causing an increase in ROS levels, JNK phosphorylation, and mitochondrial stress. Cytochrome c was then released into cytoplasm, which, in turn activated the cysteine protease pathway and ultimately induced tumor cell apoptosis, suggesting a potential use of this compound for colon cancer treatment.

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Combination of amino acid/dipeptide with ligustrazine-betulinic acid as antitumor agents

Cited by 28 publications

References 37 publications

Antimicrobial activity of Mimosa caesalpiniifolia Benth and its interaction with antibiotics against Staphylococcus aureus strains overexpressing efflux pump genes

Antimicrobial activity of Mimosa caesalpiniifolia Benth and its interaction with antibiotics against Staphylococcus aureus strains overexpressing efflux pump genes

<p>Design, Synthesis and Biological Evaluation of New HDAC1 and HDAC2 Inhibitors Endowed with Ligustrazine as a Novel Cap Moiety</p>

Novel Anthraquinone Compounds Inhibit Colon Cancer Cell Proliferation via the Reactive Oxygen Species/JNK Pathway

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