Antiproliferative and pro-apoptotic activities of 2′- and 4′-aminochalcones against tumor canine cells

Santos, Mariana Bastos dos; Pinhanelli, Vitor Caressato; Garcia, Maíra Terra; Silva, Gabriel; Baek, Seung Joon; França, Suzelei C.; Fachin, Ana Lúcia; Marins, Mozart; Regasini, Luís Octávio

doi:10.1016/j.ejmech.2017.06.049

Cited by 37 publications

(31 citation statements)

References 30 publications

(33 reference statements)

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“…Statistical analyses were carried out using one-way ANOVA multiple comparison tests followed by Tukey's HSD test 19,27 . Statistical significance difference was considered if p< 0.05.…”

Section: Discussionmentioning

confidence: 99%

“…Reagents and solvents were purchased from Merck V R (Kenilworth, NJ). Series of 20 chalcones was synthesised by Claisen-Schmidt aldol condensation reaction, according to protocol described by Santos and coauthors, with minor modifications 19,20 . Reactions were carried out at room temperature using 3.0 mmol of 4'-aminoacetophenone and 3.0 mmol of aldehydes, which were dissolved in ethanol (30 mL).…”

Section: Chemical Procedures For Synthesis Of Chalcones 1-20mentioning

confidence: 99%

“…Formazan crystals were solubilised in dimethylsulfoxide (DMSO, Sigma Aldrich V R , St. Louis, MO), and absorbance rates were measured at 562 nm in ThermoPlate V R TP Reader. Chalcones 1,6,8,9,11,17,19, and 20 had the highest antiproliferative activity and were assayed against both cell lines at seven concentrations, ranging from 1.25 to 80 lM for IC 50 values determination.…”

Section: Antiproliferative Activity Of Chalcones 1-20mentioning

confidence: 99%

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Antiproliferative activity and p53 upregulation effects of chalcones on human breast cancer cells

Santos

Anselmo

Oliveira

et al. 2019

Journal of Enzyme Inhibition and Medicinal Chemistry

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Chalcones are valuable structures for drug discovery due to their broad bioactivity spectrum. In this study, we evaluated 20 synthetic chalcones against estrogen-receptor-positive breast cancer cells (MCF-7 line) and triple-negative breast cancer (TNBC) cells (MDA-MB-231 line). Antiproliferative screening by MTT assay resulted in two most active compounds: 2-fluoro-4'-aminochalcone (11) and 3-pyridyl-4'-aminochalcone (17). Their IC 50 values ranged from 13.2 to 34.7 mM against both cell lines. Selected chalcones are weak basic compounds and maintained their antiproliferative activity under acidosis conditions (pH 6.7), indicating their resistance to ion-trapping effect. The mode of breast cancer cells death was investigated and chalcones 11 and 17 were able to induce apoptosis rather than necrosis in both lines. Antiproliferative target investigations with MCF-7 cells suggested 11 and 17 upregulated p53 protein expression and did not affect Sp1 protein expression. Future studies on chalcones 11 and 17 can define their in vivo therapeutic potential.

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“…Statistical analyses were carried out using one-way ANOVA multiple comparison tests followed by Tukey's HSD test 19,27 . Statistical significance difference was considered if p< 0.05.…”

Section: Discussionmentioning

confidence: 99%

Section: Chemical Procedures For Synthesis Of Chalcones 1-20mentioning

confidence: 99%

Section: Antiproliferative Activity Of Chalcones 1-20mentioning

confidence: 99%

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Antiproliferative activity and p53 upregulation effects of chalcones on human breast cancer cells

Santos

Anselmo

Oliveira

et al. 2019

Journal of Enzyme Inhibition and Medicinal Chemistry

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“…Our research group has been working to identify small molecules that can be used as metastasis inhibitors through the induction of p53 [ 12 , 13 ]. Prominent among these are chalcones, a group of polyphenolic compounds with an alpha-beta unsaturated ketone core moiety that exerts cytotoxic activity against different tumor cell lines through mechanisms such as cell cycle disruption, the inhibition of angiogenesis, and the induction of apoptosis [ 14 , 15 , 16 , 17 ]. In previous works using U2OS osteosarcoma cells and other tumor cell lines, we found that trans-chalcone has apoptotic activity mediated by p53 activation, in addition to regulating genes involved in cell migration and invasion [ 18 ].…”

Section: Introductionmentioning

confidence: 99%

Chalcone Derivatives 4′-Amino-1-Naphthyl-Chalcone (D14) and 4′-Amino-4-Methyl-1-Naphthyl-Chalcone (D15) Suppress Migration and Invasion of Osteosarcoma Cells Mediated by p53 Regulating EMT-Related Genes

Seba

Silva

Santos

et al. 2018

IJMS

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Osteosarcoma (OS) is a primary malignant bone tumor that mainly affects children, adolescents, and young adults. The inhibition of metastasis is a main strategy of OS therapy since the development of metastatic disease due to drug resistance remains the most important cause of death from this cancer. Considering the severe side effects of current OS chemotherapy, the identification of anti-metastatic drugs with reduced toxicity is of great interest. Chalcones are polyphenols with a basic structure consisting of an α-, β-unsaturated carbonyl system linking two aryl rings. These compounds exhibit anticancer activity against a variety of tumor cell lines through multiple mechanisms, including the regulation of the tumor-suppressor protein p53 and its target genes. An important process regulated by p53 is epithelial-mesenchymal transition (EMT), which facilitates tumor metastasis by conferring migratory and invasive properties to cancer cells. The activation of p53 can revert EMT and reduce migration and invasion. This study aimed to examine the inhibitory effects of two 4′-aminochalcones on the migration/invasion of the U2OS (p53+/+) and SAOS-2 (p53−/−) OS cell lines as well as the underlying molecular mechanisms. Cell viability was examined by MTT assay. Transwell assays were used to evaluate the migratory and invasive ability of the cells. The two 4′-aminochalcones showed low capacity to inhibit the viability of OS cells independent of p53 status, but preferentially suppressed the migration of U2OS cells and of a SAOS-2 cell line expressing p53. Invasion was strongly inhibited by both chalcones independent of p53 status. RT-PCR, zymography, and Western blot were used to study the expression of matrix metalloproteinases and EMT markers after treatment with the chalcones. The results indicated that the 4′-aminochalcone-induced antimigratory and anti-invasive effects are potentially associated with the inhibition of extracellular matrix (ECM) enzymatic degradation in OS cells and with the modulation of EMT genes. These effects probably result from the induced increase of p53 protein expression by the two chalcones. In conclusion, chalcones D14 and D15 have potential anti-metastatic activity mediated by p53 that can be exploited for OS treatment.

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“…Synthesis of BC1 was achieved by the reaction between acetovanillone (5 mmol) and benzaldehyde (5 mmol) at room temperature using ethanol as the solvent and ethanolic solution of NaOH (1.0 mol/L, 5 mL), using a protocol reported by Santos and collaborators with minor modifications [ 31 ]. The reaction mixture was stirred and monitored by successive thin-layer chromatography (TLC) analyses.…”

Section: Methodsmentioning

confidence: 99%

Investigating the Modes of Action of the Antimicrobial Chalcones BC1 and T9A

et al. 2020

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Xanthomonas citri subsp. citri (X. citri) is an important phytopathogen and causes Asiatic Citrus Canker (ACC). To control ACC, copper sprays are commonly used. As copper is an environmentally damaging heavy metal, new antimicrobials are needed to combat citrus canker. Here, we explored the antimicrobial activity of chalcones, specifically the methoxychalcone BC1 and the hydroxychalcone T9A, against X. citri and the model organism Bacillus subtilis. BC1 and T9A prevented growth of X. citri and B. subtilis in concentrations varying from 20 µg/mL to 40 µg/mL. BC1 and T9A decreased incorporation of radiolabeled precursors of DNA, RNA, protein, and peptidoglycan in X. citri and B. subtilis. Both compounds mildly affected respiratory activity in X. citri, but T9A strongly decreased respiratory activity in B. subtilis. In line with that finding, intracellular ATP decreased strongly in B. subtilis upon T9A treatment, whereas BC1 increased intracellular ATP. In X. citri, both compounds resulted in a decrease in intracellular ATP. Cell division seems not to be affected in X. citri, and, although in B. subtilis the formation of FtsZ-rings is affected, a FtsZ GTPase activity assay suggests that this is an indirect effect. The chalcones studied here represent a sustainable alternative to copper for the control of ACC, and further studies are ongoing to elucidate their precise modes of action.

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Antiproliferative and pro-apoptotic activities of 2′- and 4′-aminochalcones against tumor canine cells

Cited by 37 publications

References 30 publications

Antiproliferative activity and p53 upregulation effects of chalcones on human breast cancer cells

Antiproliferative activity and p53 upregulation effects of chalcones on human breast cancer cells

Chalcone Derivatives 4′-Amino-1-Naphthyl-Chalcone (D14) and 4′-Amino-4-Methyl-1-Naphthyl-Chalcone (D15) Suppress Migration and Invasion of Osteosarcoma Cells Mediated by p53 Regulating EMT-Related Genes

Investigating the Modes of Action of the Antimicrobial Chalcones BC1 and T9A

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