Abstract:Copper-based chemotherapeutic compounds Casiopeínas, have been presented as able to promote selective programmed cell death in cancer cells, thus being proper candidates for targeted cancer therapy. DNA fragmentation and apoptosis–in a process mediated by reactive oxygen species–for a number of tumor cells, have been argued to be the main mechanisms. However, a detailed functional mechanism (a model) is still to be defined and interrogated for a wide variety of cellular conditions before establishing settings … Show more
“…These copper complexes have been developed primarily for their action against cancerous tumors [14,15,16] in in vitro and in vivo models. Although the action mechanism is not known in detail, at the molecular level, several results support that these compounds are able to inhibit cell proliferation mainly by apoptotic pathways [15,16], that participate in redox reactions that produce reactive oxygen species [15,16] and interact directly with DNA and its constituents [17].…”
New compounds with antituberculosis activity and their combination with classic drugs have been evaluated to determine possible interactions and antagonism. The aim of this study was to evaluate the in vitro activity of Casiopeínas® copper-based compounds (CasIIIia, CasIIIEa, and CasIIgly) alone and combined with isoniazid (INH), rifampicin, or ethambutol (EMB) against resistant and susceptible Mycobacterium tuberculosis. Seventeen clinical M. tuberculosis isolates (5 multi-drug resistant and 2 resistant to INH and/or EMB) were subjected to determination of the minimal inhibitory concentration (MIC) by the resazurin microtiter assay and combination assessment by the resazurin drug combination microtiter assay. The Casiopeínas® alone showed a remarkable effect against resistant isolates with MIC values from 0.78 to 12.50 μg/ml. Furthermore, a synergistic effect mainly with EMB is shown for both resistant and susceptible clinical isolates. Casiopeínas® are promising candidates for future investigation into the development of antituberculosis drugs, being one of the first examples of essential metal-based drugs used in this field.
“…These copper complexes have been developed primarily for their action against cancerous tumors [14,15,16] in in vitro and in vivo models. Although the action mechanism is not known in detail, at the molecular level, several results support that these compounds are able to inhibit cell proliferation mainly by apoptotic pathways [15,16], that participate in redox reactions that produce reactive oxygen species [15,16] and interact directly with DNA and its constituents [17].…”
New compounds with antituberculosis activity and their combination with classic drugs have been evaluated to determine possible interactions and antagonism. The aim of this study was to evaluate the in vitro activity of Casiopeínas® copper-based compounds (CasIIIia, CasIIIEa, and CasIIgly) alone and combined with isoniazid (INH), rifampicin, or ethambutol (EMB) against resistant and susceptible Mycobacterium tuberculosis. Seventeen clinical M. tuberculosis isolates (5 multi-drug resistant and 2 resistant to INH and/or EMB) were subjected to determination of the minimal inhibitory concentration (MIC) by the resazurin microtiter assay and combination assessment by the resazurin drug combination microtiter assay. The Casiopeínas® alone showed a remarkable effect against resistant isolates with MIC values from 0.78 to 12.50 μg/ml. Furthermore, a synergistic effect mainly with EMB is shown for both resistant and susceptible clinical isolates. Casiopeínas® are promising candidates for future investigation into the development of antituberculosis drugs, being one of the first examples of essential metal-based drugs used in this field.
“…IPA has been extensively used in biomedical research (having almost 9,000 citations (7)) to analyze big data because its Ingenuity Knowledge Base is the largest curated database of biological and chemical interactions, extracted from the scientific literature (7,14). By using IPA's bioinformatics tools to search the knowledge base, we have identified several potential novel molecular targets for the treatment of SNHL and prioritized human testing of drugs that have shown promise in animal studies.…”
Metabolomic and network analysis of the existing pharmacotherapies for SNHL has pointed to and prioritized a number of potential novel targets for treatment of SNHL.
“…The need to carry out physicochemical studies in order to determine the aggregation properties of this compounds is of great importance since other compounds of the family of the Casiopeínas have also shown antitumor and anti-protozoan activity [7, 24–26]. …”
Section: Resultsmentioning
confidence: 99%
“…Experimental observations showed that different members of the family of the Casiopeínas present nuclease activity in contact with DNA, comparable to that shown by other metal complexes [6]. These results allowed to design and perform an experiment of the whole genetic expression of tumor cells exposed to Casiopeínas, where it was found that particular pathways related with the cell cycle, gene expression, cellular growth, proliferation and cell death were affected, all of them related with oxidative stress and DNA damage [7]. Fig.…”
From studies using different experimental techniques employed to determine the presence of aggregates e.g. isothermal titration calorimetry, surface tension, electrical conductivity, UV–Vis spectrophotometry, dynamic and static light scattering, it is clearly demonstrated that the compound [Cu(4, 4′-dimethyl-2, 2′-bipyridine)(acetylacetonato)H2O]NO3 (Casiopeína III-ia), promising member of a family of new generation compounds for cancer treatment, is able to auto associate in aqueous media. Physicochemical properties associated with the formation of the aggregates were determined in pure water and in phosphate buffer media in order to simulate physiological conditions. From isothermal titration calorimetry and electrical conductivity measurements we calculated the dissociation constant of the aggregates, K
D. For pure water the values obtained in both techniques are 2.73 × 10−4 and 5.93 × 10−4 M respectively while for the buffer media we obtained 4.61 × 10−4 and 1.57 × 10−3 M. The enthalpy of dissociation, ∆H
D, calculated from the calorimetric data shows that the presence of the phosphate ions has an energetic effect on the aggregate stability since in pure water a value of 18.79 kJ mol−1 was obtained in comparison with the buffer media where a value 4 times bigger was found (70.48 kJ mol−1). With the data collected from these techniques the number of monomers calculated which participate in the formation of the aggregates is around two. From our surface tension, electrical conductivity and UV–Vis spectrophotometry measurements the critical aggregate concentration, cac, was determined. For each technique specific concentration ranges were obtained but we can summarize that the cac in pure water is between 3 and 3.5 mM and for the buffer media is between 3.5 and 4 mM. Dynamic light scattering measurements provide us with the hydrodynamic diameter of the aggregates and from static light scattering measurements we determined the molecular weight of the Casiopeína III-ia aggregates to be of 1000.015 g mol−1 which is two times the molecular weight of the Casiopeína III-ia molecule. This value is in agreement with the number of monomers which participate in the formation of the aggregates obtained from isothermal titration calorimetry and electrical conductivity data analysis.
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