New Bis copper complex ((Z) -4 - ((4-chlorophenyl) amino) -4-oxobut-2-enoyl) oxy): Cytotoxicity in 4T1 cells and their toxicogenic potential in Swiss mice

Oliveira, Edwin José Torres de; Pessatto, Lucas Roberto; Freitas, Raquel Oliveira Nascimento de; Pelizaro, Bruno Ivo; Rabacow, Ana Paula Maluf; Vani, Juliana Miron; Monreal, Antônio Carlos Duenhas; Mantovani, Mário; Azevedo, Ricardo Bentes; Antoniolli-Silva, Andréia Conceição Milan Brochado; Gomes, Roberto da Silva; Oliveira, Rodrigo Juliano

doi:10.1016/j.taap.2018.08.004

Cited by 8 publications

(5 citation statements)

References 60 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Weight loss during the experimental period and changes in the relative weight of organs are important indicators of toxicity. 45,46 Also, no clinical changes were observed, such as dryness of the mucosa, opacity, and bristles of hair, behavioral changes, skin lesions, lethargy, changes in ambulation (locomotor hypoactivity), tremors, decreased food and water intake, and consequently, gradual reduction in weight, and death, which are important indicators of toxicity (OECD 425−2008). Resorcinolic lipids, analogs of cytosporones, do not have toxicity and, therefore, did not change these parameters, as is the case with AMS35AA, 8,47 and AMS049.…”

Section: Discussionmentioning

confidence: 99%

“…These results suggest that AMS35BB does not induce toxicity. Weight loss during the experimental period and changes in the relative weight of organs are important indicators of toxicity. , …”

Section: Discussionmentioning

confidence: 99%

“…According to Rabacow et al., , AMS35AA can induce cell death in tumor cells (MCF-7). This compound is cytotoxic (IC50 = 54 μM); caused genomic damage, confirmed by increased comet frequency and expression of ATR, p53, p21, and GADD45 genes; and induced cell cycle retention in G2/M and reduction of cells in S phase.…”

Section: Discussionmentioning

confidence: 99%

“…55 In mitochondria, it interacts with Bcl-2, which induces a conformational change, triggering the release of Cytochrome C and, finally, apoptosis. 62,63 According to Rabacow et al, 45,46 AMS35AA can induce cell death in tumor cells (MCF-7). This compound is cytotoxic (IC50 = 54 μM); caused genomic damage, confirmed by increased comet frequency and expression of ATR, p53, p21, and GADD45 genes; and induced cell cycle retention in G2/M and reduction of cells in S phase.…”

Section: Discussionmentioning

confidence: 99%

See 3 more Smart Citations

Chemotherapeutic Mechanism of Action of the Synthetic Resorcinolic Methyl 3,5-dimethoxy-2-octanoylbenzoate

Correa,

das Neves,

Oliveira

et al. 2024

Chem. Res. Toxicol.

Self Cite

View full text Add to dashboard Cite

Resorcinolic lipids are described as potential examples of selective chemotherapeutic adjuvants that can enhance the effects of cyclophosphamide (CYC) while promoting cell death without causing DNA damage. Therefore, the current study attempted to describe how the resorcinolic lipid methyl 3,5-dimethoxy-2-octanoylbenzoate (AMS35BB) interacted with DNA (DNA docking) and how this compound affected genetic toxicology models and other biological characteristics when combined with CYC. We observed that AMS35BB, used alone (7.5 and 10 mg/kg), increases the frequency of genomic damage (comet assay) but not chromosomal damage (micronuclei assay), lowers phagocytosis, and promotes cell death in Swiss male mice. When used in association with CYC, AMS35BB can reduce the risk of genomic damage by up to 33.8% as well as chromosomal damage, splenic phagocytosis, cell death, and lymphocyte frequency. Molecular docking showed that AMS35BB had a higher affinity than the active metabolite of CYC for binding to the DNA double helix major groove. As a result, AMS35BB has the potential to be both an adjuvant when used in association with CYC and a therapeutic candidate for the development of a selective chemotherapeutic drug.

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

See 2 more Smart Citations

Chemotherapeutic Mechanism of Action of the Synthetic Resorcinolic Methyl 3,5-dimethoxy-2-octanoylbenzoate

Correa,

das Neves,

Oliveira

et al. 2024

Chem. Res. Toxicol.

Self Cite

View full text Add to dashboard Cite

show abstract

“…1,4-Dioxobutenyl and 4-aminoantipyrine moieties have a variety of pharmacological activities. They are viable candidates for the synthesis of new chemotherapeutic agents. , More specifically, the 1,4-dioxo-butenyl group has presented promising biological activities in the treatment of cancer. , In fact, previous studies have shown that the synthesis of compounds that include fragments of 4-aminoantipyrine and maleimide has antibacterial and analgesic properties, as well as a promising cytotoxicity profile in preclinical models. − Furthermore, previous studies have shown the use of cantharidin, a terpenoid secreted by many species of blister beetles, and its derivatives to treat leukemia, melanoma, liver, lung, and breast cancer (Figure ). , …”

Section: Introductionmentioning

confidence: 99%

ZIM, a Norbornene Derived from 4-Aminoantipyrine, Induces DNA Damage and Cell Death but in Association Reduces the Effect of Commercial Chemotherapeutics

Oliveira

Silveira

Neves

et al. 2022

Chem. Res. Toxicol.

Self Cite

View full text Add to dashboard Cite

Cancer incidence is increasing, and the drugs are not very selective. These drugs cause adverse effects, and the cells become resistant. Therefore, new drugs are needed. Here, we evaluated the effects of ZIM, a candidate for chemotherapy, and 4-AA alone and in association with commercial chemotherapeutic agents. Subsequently, the results of ZIM and 4-AA were compared. Male Swiss mice were treated with doses of 12, 24, or 48 mg/kg ZIM or 4-AA alone or in association with cisplatin (6 mg/kg), doxorubicin (16 mg/kg), and cyclophosphamide (100 mg/kg). Biometric parameters, DNA damage (comet and micronuclei), cell death, and splenic phagocytosis were evaluated. DNA docking was also performed to confirm the possible interactions of ZIM and 4-AA with DNA. 4-AA has been shown to have low genotoxic potential, increase the frequency of cell death, and activate phagocytosis. ZIM causes genomic and chromosomal damage in addition to causing cell death and activating phagocytosis. In association with chemotherapeutical agents, both 4-AA and ZIM have a chemopreventive effect and, therefore, reduce the frequency of DNA damage, cell death, and splenic phagocytosis. The association of 4-AA and ZIM with commercial chemotherapeutic agents increased the frequency of lymphocytes compared to chemotherapeutic agents alone. Molecular docking demonstrated that ZIM has more affinity for DNA than 4-AA and its precursors (1 and 2). This was confirmed by the lower interaction energy of the complex (−119.83 kcal/mol). ZIM can break the DNA molecule and, therefore, its chemotherapeutic effect can be related to DNA damage. It is considered that ZIM has chemotherapeutic potential. However, it should not be used in combination with cisplatin, doxorubicin, and cyclophosphamide as it reduces the effects of these drugs.

show abstract

Design, synthesis and in vivo evaluation of 1,4-dioxo-2-butenyl aryl amine derivatives as a promising anti-inflammatory drug prototype

Silveira

Moslaves

Muller

et al. 2022

Bioorganic Chemistry

View full text Add to dashboard Cite

New Bis copper complex ((Z) -4 - ((4-chlorophenyl) amino) -4-oxobut-2-enoyl) oxy): Cytotoxicity in 4T1 cells and their toxicogenic potential in Swiss mice

Cited by 8 publications

References 60 publications

Chemotherapeutic Mechanism of Action of the Synthetic Resorcinolic Methyl 3,5-dimethoxy-2-octanoylbenzoate

Chemotherapeutic Mechanism of Action of the Synthetic Resorcinolic Methyl 3,5-dimethoxy-2-octanoylbenzoate

ZIM, a Norbornene Derived from 4-Aminoantipyrine, Induces DNA Damage and Cell Death but in Association Reduces the Effect of Commercial Chemotherapeutics

Design, synthesis and in vivo evaluation of 1,4-dioxo-2-butenyl aryl amine derivatives as a promising anti-inflammatory drug prototype

Contact Info

Product

Resources

About