High anticancer potency on tumor cells of dehydroabietylamine Schiff-base derivatives and a copper(II) complex

Zhao, Fengyi; Wang, Weifan; Lu, Weiying; Xu, Li; Yang, Shilong; Cai, Xu‐Min; Zhou, Mengyi; Meng, Lei; Ma, Mengtao; Xu, Haijun; Cao, Fuliang

doi:10.1016/j.ejmech.2018.01.041

Cited by 71 publications

(22 citation statements)

References 43 publications

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“…Ever since the successful synthesis and characterization of imines by Hugo Schiff in 1864, they have been investigated extensively for their biological activities, [ 26 ] and anticancer potential. [ 27,28 ] We, therefore, synthesized seven Schiff‐base‐type noscapine analogues (Scheme 1), characterized them with NMR and mass spectroscopy, tested their in‐vitro antiproliferative and anticlonogenic efficacy against the TNBC cell line, MDA‐MB‐231, and systematically elucidated a possible molecular mechanism of action of one of the most potent analogues, 9‐PAN ( 5c ), that inhibited the cell proliferation with an IC 50 of 20 ± 1.25 µ m (Figure 1b). Cancer cells propagate by colonizing in different parts of the body.…”

Section: Discussionmentioning

confidence: 99%

9-PAN promotes tubulin- and ROS-mediated cell death in human triple-negative breast cancer cells

Verma

Nagireddy

Prassanawar

et al. 2020

Journal of Pharmacy and Pharmacology

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Objectives To examine the antiproliferative effect of a rationally designed, novel noscapine analogue, 9-((perfluorophenyl)methylene) aminonoscapine, '9-PAN') on MDA-MB-231 breast cancer cell line, and to elucidate the underlying mechanism of action. Methods The rationally designed Schiff base-containing compound, 9-PAN, was characterized using IR, NMR and mass spectra analysis. The effect of the compound on cell viability was studied using an MTT assay. Cell cycle and cell death analyses were performed using flow cytometry. Binding interactions of 9-PAN with tubulin were studied using spectrofluorometry. Reactive oxygen species (ROS) generation and mitochondrial membrane potential (MMP) were investigated using the probes, DCFDA and rhodamine-123, respectively. Immunofluorescence imaging was used to visualize cellular microtubules. Key findings 9-PAN inhibited cell proliferation (IC 50 of 20 AE 0.3 µM) and colony formation (IC 50 , 6.2 AE 0.3 µM) by arresting the cells at G 2 /M phase of the cell cycle. It bound to tubulin in a concentration-dependent manner without considerably altering the tertiary conformation of the protein or the polymer mass of the microtubules in vitro. The noscapinoid substantially damaged cellular microtubule network and induced cell death, facilitated by elevated levels of ROS. Conclusions 9-PAN exerts its antiproliferative effect by targeting tubulin and elevating ROS level in the cells.

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Section: Discussionmentioning

confidence: 99%

9-PAN promotes tubulin- and ROS-mediated cell death in human triple-negative breast cancer cells

Verma

Nagireddy

Prassanawar

et al. 2020

Journal of Pharmacy and Pharmacology

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“…As can be seen from Figure 3, the toxicity of coumarin-3formamide derivatives (2-11) is lower than DOX (4.40 ± 0.55 μM) [34] against HUVEC cells, but the antineoplastic activities of all compounds against HeLa, HepG2, MCF-7, and A549 cells are lower than against HeLa cells may be due to the presence of the imidazole ring in its structure. The azole compounds are aromatic and rich in electrons, so these compounds can interact with enzymes, DNA, and so forth, thus exhibiting various biological activities such as anticancer, antibacterial, and antiviral.…”

Section: Antitumor Activitiesmentioning

confidence: 93%

Synthesis, antiproliferative activities, and DNA binding of coumarin‐3‐formamido derivatives

Shi

Chen

et al. 2020

Archiv der Pharmazie

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Ten coumarin‐3‐formamido derivatives, N‐benzyl‐coumarin‐3‐carboxamide (2), N‐fluorobenzyl‐coumarin‐3‐carboxamide (3–5), N‐methoxybenzyl‐coumarin‐3‐carboxamide (6–8), N‐((1‐methyl‐1H‐imidazol‐5‐yl)methyl)‐coumarin‐3‐carboxamide (9), N‐(thiophen‐2‐ylmethyl)‐coumarin‐3‐carboxamide (10), and N‐(furan‐2‐ylmethyl)‐coumarin‐3‐carboxamide (11), were synthesized and characterized. Compound 5 crystallizes in a monoclinic system P21/c space group with four chemical formulas in a unit cell; molecules of compound 5 are self‐assembled into a two‐dimensional supramolecular structure by intermolecular hydrogen bonds and C⋯C π stacking. The potential anticancer effects of these compounds on HeLa (cervical carcinoma), MCF‐7 (breast), A549 (lung), HepG2 (liver), and human umbilical vein (HUVEC) cells were examined. Compared with compounds 1–8 and 10–11, compound 9 exhibits potent in vitro cytotoxicity against HeLa cells and lower cytotoxicity against normal cells. Therefore, further in‐depth investigations of compound 9 were performed. Absorption titration experiments and fluorescence spectroscopy studies suggested that compound 9 binds to DNA through the intercalation mode.

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“…Therefore, many quinazoline derivatives have been synthesized, such as those with ether, azo compound, and amine linkages, via the substitution of different sites in the quinazoline core to enhance the anti-cancer potency ( Yin et al., 2017 ; Yang et al., 2018 ; Liu et al., 2019 ). Furthermore, the Schiff base group (C = N), a crucial functional group, has been revealed to markedly improve druggability because of its wide range of pharmacological effects, lower toxicity, and maximal effects ( Makawana et al., 2014 ; Zhao et al., 2018 ; Sâmia et al., 2019 ). To date, no quinazoline-phenyl chlormethine conjugates bearing a Schiff base linker have been developed as anti-tumor agent.…”

Section: Introductionmentioning

confidence: 99%

Synthesis of a New Phenyl Chlormethine-Quinazoline Derivative, a Potential Anti-Cancer Agent, Induced Apoptosis in Hepatocellular Carcinoma Through Mediating Sirt1/Caspase 3 Signaling Pathway

Song

et al. 2020

Front. Pharmacol.

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Quinazoline derivatives display multiple pharmacological activities and target various biological receptors. Based on the skeleton of quinazoline core, we designed and synthesized three new quinazoline-phenyl chlormethine conjugates (I-III) bearing a Schiff base (C = N) linker, and investigated their anti-tumor effects on HepG2-xenografted tumor and human cancer cell line HepG2. Among these compounds, compound II showed better inhibitory effect against HepG2 cells. In the present study, TUNEL staining, western blot, molecular docking, and siRNA were used to investigate the inhibitory mechanism of compound II towards hepatoma. Compound II inhibited HepG2-xenografted tumor growth in nude mice. Moreover, Compound II not only up-regulated Bax/Bcl-2 ratio and active-caspase 3 level, but also down-regulated Sirt1 expression and its activity, as well as PGC-1a expression. Furthermore, compound II also significantly suppressed the promotion of HepG2 cell proliferation, as evidenced by MTT assay and lactate dehydrogenase (LDH) release assay. Of note, the cytotoxicity of Compound II on HepG2 cells mainly via regulating Sirt1/caspase 3 signaling pathway, consisting with the results in vivo. Intriguingly, z-DEVD-FMK, a caspase 3 inhibitor, almost abolished the inhibitory effects of compound II. Of note, knockdown of caspase 3 by siRNA significantly reversed the inhibitory effect of compound II on HepG2. Interestingly, compound II directly bonded to Sirt1, indicating that Sirt1 might be a promising therapeutic target of compound II. In summary, our findings reveal that compound II, a new synthetical phenyl chlormethine-quinazoline derivative, contributes to the apoptosis of HepG2 cells both in vivo and in vitro through mediating Sirt1/caspase 3 singling pathway. These findings demonstrate that compound II may be a new potent agent against hepatocellular carcinoma.

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High anticancer potency on tumor cells of dehydroabietylamine Schiff-base derivatives and a copper(II) complex

Cited by 71 publications

References 43 publications

9-PAN promotes tubulin- and ROS-mediated cell death in human triple-negative breast cancer cells

9-PAN promotes tubulin- and ROS-mediated cell death in human triple-negative breast cancer cells

Synthesis, antiproliferative activities, and DNA binding of coumarin‐3‐formamido derivatives

Synthesis of a New Phenyl Chlormethine-Quinazoline Derivative, a Potential Anti-Cancer Agent, Induced Apoptosis in Hepatocellular Carcinoma Through Mediating Sirt1/Caspase 3 Signaling Pathway

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