Diaryl sulfide analogs of combretastatin A-4: Toxicogenetic, immunomodulatory and apoptotic evaluations and prospects for use as a new chemotherapeutic drug

Carvalho, Pamela Castilho de; Santos, Edson A. dos; Schneider, Beatriz Ursinos Catelán; Matuo, Renata; Pesarini, João Renato; Cunha-Laura, Andréa Luiza; Monreal, Antônio Carlos Duenhas; Lima, Dênis Pires de; Antoniolli, Andréia Conceição Milan Brochado; Oliveira, Rodrigo Juliano

doi:10.1016/j.etap.2015.08.028

Cited by 30 publications

(23 citation statements)

References 23 publications

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“…Next, the slide was fixed in Carnoy’s solution for 5 min and was then subjected to a decreasing series of ethanol concentrations (95-25%), washed with McIlvaine’s buffer for 5 min, stained with 0.01% acridine orange for 5 min and washed again with buffer. Dying cells were identified through an analysis of the DNA fragmentation patterns, according to Carvalho et al (2015) and Navarro et al (2014) .…”

Section: Methodsmentioning

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: Methodsmentioning

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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“…Also, there is an important need to find compounds without toxicity but with the ability to potentiate the antitumor effects of commercial chemotherapy and/or increase their selectivity ( Navarro et al. , 2014 ; Carvalho et al. , 2015 ; Oliveira et al.…”

Section: Introductionmentioning

confidence: 99%

Cardanol: toxicogenetic assessment and its effects when combined with cyclophosphamide

et al. 2016

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Cardanol is an effective antioxidant and is a compound with antimutagenic and antitumoral activity. Here, we evaluated the genotoxic and mutagenic potential of saturated side chain cardanol and its effects in combination with cyclophosphamide in preventing DNA damage, apoptosis, and immunomodulation. Swiss mice were treated with cardanol (2.5, 5 and 10 mg/kg) alone or in combination with cyclophosphamide (100 mg/kg). The results showed that cardanol is an effective chemopreventive compound, with damage reduction percentages that ranged from 18.9 to 31.76% in the comet assay and from 45 to 97% in the micronucleus assay. Moreover, cardanol has the ability to reduce the frequency of apoptosis induced by cyclophosphamide. The compound did not show immunomodulatory activity. A final interpretation of the data showed that, despite its chemoprotective capacity, cardanol has a tendency to induce DNA damage. Hence, caution is needed if this compound is used as a chemopreventive agent. Also, this compound is likely not suitable as an adjuvant in chemotherapy treatments that use cyclophosphamide.

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“…[34][35][36] The capacity of these compounds to form bonds with cell proteins by modifying protein dynamics can interrupt the cell cycle and thus trigger apoptosis. [37] Frequently, apoptosis is unleashed by the intrinsic pathway activated by intracellular stress conditions. [38][39][40] Studies performed by Wang and coworkers (2001) showed that diaryl disulfide (1) and the thiosulfonate (4) were cytotoxicity against human leukemia RPMI 8402 cells, stimulating DNA scission mediated by type II topoisomerase (TOP2) via S-thiolation.…”

Section: Antiproliferative Activitiesmentioning

confidence: 99%

S‐(4‐Methoxyphenyl)‐4‐methoxybenzenesulfonothioate as a Promising Lead Compound for the Development of a Renal Carcinoma Agent

et al. 2020

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Organosulfur compounds show cytotoxic potential towards many tumor cell lines. Disulfides and thiosulfonates act through apoptotic processes, inducing proteins associated with apoptosis, endoplasmic reticulum stress, and the unfolded protein response. Three p‐substituted symmetric diaryl disulfides and three diaryl thiosulfonates were synthesized and analyzed for inhibition of tubulin polymerization and for human cancer cell cytotoxic activity against seven tumor cell lines and a non‐tumor cell line. S‐(4‐methoxyphenyl)‐4‐methoxybenzenesulfonothioate (6) exhibited inhibition of tubulin polymerization and showed the best antiproliferative potential, especially against the 786‐0 cell line, being six times more selective as compared with the non‐tumor cell line. In addition, compound 6 was able to activate caspase‐3 after 24 and 48 h treatments of the 786‐0 cell line and induced cell‐cycle arrest in the G2/M stage at the highest concentration evaluated at 24 and 48 h. Compound 6 was able to cause complete inhibition of proliferation, inducing the death of 786‐0 cells, by increasing the number of cells at G2/M and greater activation of caspase‐3.

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Diaryl sulfide analogs of combretastatin A-4: Toxicogenetic, immunomodulatory and apoptotic evaluations and prospects for use as a new chemotherapeutic drug

Cited by 30 publications

References 23 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

Cardanol: toxicogenetic assessment and its effects when combined with cyclophosphamide

S‐(4‐Methoxyphenyl)‐4‐methoxybenzenesulfonothioate as a Promising Lead Compound for the Development of a Renal Carcinoma Agent

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