4-Nerolidylcatechol and its synthetic analogues: Antioxidant activity and toxicity evaluation

Cunha, Carla Rosane Mendanha da; Neto, Sebastião Antônio Mendanha; Silva, Cláudio Carlos da; Cortez, Alane Pereira; Gomes, Marcelo do Nascimento; Martins, Fabiula Ines; Alonso, Antônio; Rezende, Kênnia Rocha; Menegatti, Ricardo; Magalhães, Mariana T.Q. de; Valadares, Marize Campos

doi:10.1016/j.ejmech.2012.12.028

Cited by 14 publications

(4 citation statements)

References 25 publications

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“…According to Rundell et al (2003) , genotoxic damage is likely to undergo repair, whereas mutagenic damage is not, with changes becoming fixed in the genetic material as mutations. Such occurrence is not uncommon in preclinical chemoprevention experiments, both with natural products ( Synder and Gillies, 2002 ; Cunha et al , 2005 ; Rodeiro et al , 2006 ; Hoshina et al , 2013 ; Mendanha da Cunha et al , 2013 ; Luo et al , 2015 ) and with synthetic compounds ( Zhan et al , 2008 ; Cao et al , 2015 ; Frolova et al , 2015 ; de Araújo et al , 2017 ). Although there are significant differences in the frequency of micronuclei between the negative control group and the groups treated with IR-01, Vaz et al (2016) describes that this isolated fact does not necessarily imply in toxicogenetic damage.…”

Section: Discussionmentioning

confidence: 99%

Assessment of genetic integrity, splenic phagocytosis and cell death potential of (Z)-4-((1,5-dimethyl-3-oxo-2-phenyl-2,3dihydro-1H-pyrazol-4-yl) amino)-4-oxobut-2-enoic acid and its effect when combined with commercial chemotherapeutics

et al. 2018

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The increased incidence of cancer and its high treatment costs have encouraged the search for new compounds to be used in adjuvant therapies for this disease. This study discloses the synthesis of (Z)-4-((1,5-dimethyl-3-oxo-2-phenyl-2,3dihydro-1H-pyrazol-4-yl) amino)-4-oxobut-2-enoic acid (IR-01) and evaluates not only the action of this compound on genetic integrity, increase in splenic phagocytosis and induction of cell death but also its effects in combination with the commercial chemotherapeutic agents doxorubicin, cisplatin and cyclophosphamide. IR-01 was designed and synthesized based on two multifunctionalyzed structural fragments: 4-aminoantipyrine, an active dipyrone metabolite, described as an antioxidant and anti-inflammatory agent; and the pharmacophore fragment 1,4-dioxo-2-butenyl, a cytotoxic agent. The results indicated that IR-01 is an effective chemoprotector because it can prevent clastogenic and/or aneugenic damage, has good potential to prevent genomic damage, can increase splenic phagocytosis and lymphocyte frequency and induces cell death. However, its use as an adjuvant in combination with chemotherapy is discouraged since IR-01 interferes in the effectiveness of the tested chemotherapeutic agents. This is a pioneer study as it demonstrates the chemopreventive effects of IR-01, which may be associated with the higher antioxidant activity of the precursor structure of 4-aminoantipyrine over the effects of the 1,4-dioxo-2-butenyl fragment.

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Section: Discussionmentioning

confidence: 99%

Assessment of genetic integrity, splenic phagocytosis and cell death potential of (Z)-4-((1,5-dimethyl-3-oxo-2-phenyl-2,3dihydro-1H-pyrazol-4-yl) amino)-4-oxobut-2-enoic acid and its effect when combined with commercial chemotherapeutics

et al. 2018

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“…Polyphenols with excellent antioxidant properties have been used in many kinds of food production (Li & Mattison, 2017; Trošt et al., 2016). Nevertheless, most of the polyphenol antioxidants used have been synthesized industrially at present, which may cause toxic effects after long‐term consumption (Mendanha da Cunha et al., 2013; Zhao et al., 2020). Caffeic acid (3,4‐dihydroxycinnamic acid [CA]) is an acknowledged natural phenol found in herbaceous parts of vegetables, fruits, tubers, and seeds, which has a synergistic effect on antioxidant capacity (Leonardis & Macciola, 2003; J. Liu et al., 2017).…”

Section: Introductionmentioning

confidence: 99%

Synergistic effect of docosahexaenoic acid or conjugated linoleic acid with caffeic acid on ameliorating oxidative stress of HepG2 cells

Liu

Bian

Luo

et al. 2021

Journal of Food Science

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Exploring the synergistic effect of docosahexaenoic acid (DHA) or conjugated linoleic acid (CLA) with caffeic acid (CA) on ameliorating oxidative stress, thereby introducing CA to DHA or CLA will contribute significantly to enhance the bioactivity. We observed that DHA or CLA with CA promoted the recovery of intact individual morphology and the decline of cavities inside the nucleus and apoptosis under the observation of confocal laser scanning microscopy and fluorescent inverted microscope. The activity of intracellular antioxidant enzymes catalase (CAT) and glutathione peroxidase (GSH‐Px), lactate dehydrogenase (LDH) leakage, pyruvate and malondialdehyde and reactive oxygen species (ROS), cellular morphology, and cell cycle were analyzed. Our results showed that DHA or CLA with CA enhanced the activity of CAT and GSH‐Px, decreased LDH leakage and the number of apoptotic, significantly inhibited (ROS‐induced cellular injury. Cell arrest in G1 and G2 phase during cell mitosis was reduced by the measurement of flow cytometry. DHA or CLA combined with CA could markedly strengthen the free radical scavenging and endogenous antioxidant defense capacity on HepG2 cells. This study provides a new direction in the application of synergies to antioxidant compounds. Practical Application Caffeic acid (CA) can synergize with docosahexaenoic acid (DHA) or conjugated linoleic acid (CLA) to enhance antioxidant capacity. This study highlighted an effect of ameliorating oxidative stress injury DHA or CLA with CA on HepG2 cells. The data indicated that DHA or CLA with CA might be used to relieve oxidative stress damage.

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“…(Piperaceae) (Cunha et al. 2013 ). Several studies have demonstrated the in vitro and in vivo antioxidant activity of 4-NRC using different experimental models (Desmarchelier et al.…”

Section: Introductionmentioning

confidence: 99%

4-Nerolidylcatechol: apoptosis by mitochondrial mechanisms with reduction in cyclin D1 at G0/G1 stage of the chronic myelogenous K562 cell line

Benfica

Ávila

Rodrigues

et al. 2017

Pharmaceutical Biology

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Context: 4-Nerolidylcatechol (4-NRC) has showed antitumor potential through apoptosis. However, its apoptotic mechanisms are still unclear, especially in leukemic cells.Objectives: To evaluate the cytotoxic potential of 4-NRC and its cell death pathways in p53-null K562 leukemic cells.Materials and methods: Cytotoxicity of 4-NRC (4.17–534.5 μM) over 24 h of exposure was evaluated by MTT assay. 4-NRC-induced apoptosis in K562 cells was investigated by phosphatidylserine (PS) externalization, cell cycle, sub-G1, mitochondrial evaluation, cytochrome c, cyclin D1 and intracellular reactive oxygen species (ROS) levels, and caspase activity analysis.Results: IC50 values obtained were 11.40, 27.31, 15.93 and 15.70 μM for lymphocytes, K562, HL-60 and Jurkat cells, respectively. In K562 cells, 4-NRC (27 μM) promoted apoptosis as verified by cellular morphological changes, a significant increase in PS externalization and sub-G1 cells. Moreover, it significantly arrested the cells at the G0/G1 phase due to a reduction in cyclin D1 expression. These effects of 4-NRC also significantly promoted a reduction in mitochondrial activity and membrane depolarization, accumulation of cytosolic cytochrome c and ROS overproduction. Additionally, it triggered an increase in caspases -3/7, -8 and -9 activities. When the cells were pretreated with N-acetyl-l-cysteine ROS scavenger, 4-NRC-induced apoptosis was partially blocked, which suggests that it exerts cytotoxicity though not exclusively through ROS-mediated mechanisms.Discussion and conclusion: 4-NRC has antileukemic properties, inducing apoptosis mediated by mitochondrial-dependent mechanisms with cyclin D1 inhibition. Given that emerging treatment concepts include novel combinations of well-known agents, 4-NRC could offer a promising alternative for chemotherapeutic combinations to maximize tumour suppression.

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4-Nerolidylcatechol and its synthetic analogues: Antioxidant activity and toxicity evaluation

Cited by 14 publications

References 25 publications

Assessment of genetic integrity, splenic phagocytosis and cell death potential of (Z)-4-((1,5-dimethyl-3-oxo-2-phenyl-2,3dihydro-1H-pyrazol-4-yl) amino)-4-oxobut-2-enoic acid and its effect when combined with commercial chemotherapeutics

Assessment of genetic integrity, splenic phagocytosis and cell death potential of (Z)-4-((1,5-dimethyl-3-oxo-2-phenyl-2,3dihydro-1H-pyrazol-4-yl) amino)-4-oxobut-2-enoic acid and its effect when combined with commercial chemotherapeutics

Synergistic effect of docosahexaenoic acid or conjugated linoleic acid with caffeic acid on ameliorating oxidative stress of HepG2 cells

4-Nerolidylcatechol: apoptosis by mitochondrial mechanisms with reduction in cyclin D1 at G0/G1 stage of the chronic myelogenous K562 cell line

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