123 research outputs found
Metal-based compounds containing selenium: An appealing approach towards novel therapeutic drugs with anticancer and antimicrobial effects
In recent years, both metal-based complexes and selenium-containing compounds have been widely explored for
their therapeutic properties due to their roles in biological processes and modulation of diverse molecular tar-
gets. However, despite their growing interest, there is no review to date that covers the potential use of the
combination of these entities to design new therapeutic derivatives. This review highlights the latest achieve-
ments in this particular field, with a focus on compounds with anticancer and/or antimicrobial properties. With
this aim, the formation of coordination compounds including several metals bearing selenium either with direct
interaction with the metal center or as part of the organic ligand elsewhere is covered. Besides, coordination
compounds with a Se(IV) center have been assessed. The biological properties of several selenium-containing
organometallic complexes have also been discussed, including metallocenes, half-sandwich complexes, and
compounds with N-heterocyclic carbenes, CO, and π-ligands, and other σ-bonded entities. The information
compiled in this review may be helpful to design and develop novel, more potent, and safer metal-based com-
pounds for the treatment of several pathologies
Small molecules containing chalcogen elements (S, Se, Te) as new warhead to fight neglected tropical diseases
Neglected tropical diseases (NTDs) encompass a group of infectious diseases with a protozoan etiology, high
incidence, and prevalence in developing countries. As a result, economic factors constitute one of the main
obstacles to their management. Endemic countries have high levels of poverty, deprivation and marginalization
which affect patients and limit their access to proper medical care. As a matter of fact, statistics remain un-
collected in some affected areas due to non-reporting cases. World Health Organization and other organizations
proposed a plan for the eradication and control of the vector, although many of these plans were halted by the
COVID-19 pandemic. Despite of the available drugs to treat these pathologies, it exists a lack of effectiveness
against several parasite strains. Treatment protocols for diseases such as American trypanosomiasis (Chagas
disease), leishmaniasis, and human African trypanosomiasis (HAT) have not achieved the desired results. Un-
fortunately, these drugs present limitations such as side effects, toxicity, teratogenicity, renal, and hepatic
impairment, as well as high costs that have hindered the control and eradication of these diseases. This review
focuses on the analysis of a collection of scientific shreds of evidence with the aim of identifying novel chalcogen-
derived molecules with biological activity against Chagas disease, leishmaniasis and HAT. Compounds illustrated
in each figure share the distinction of containing at least one chalcogen element. Sulfur (S), selenium (Se), and
tellurium (Te) have been grouped and analyzed in accordance with their design strategy, chemical synthesis
process and biological activity. After an exhaustive revision of the related literature on S, Se, and Te compounds,
183 compounds presenting excellent biological performance were gathered against the different causative agents
of CD, leishmaniasis and HAT
Novel methylselenoesters induce programed cell death via entosis in pancreatic cancer cells
Redox active selenium (Se) compounds have gained substantial attention in the last decade
as potential cancer therapeutic agents. Several Se compounds have shown high selectivity and
sensitivity against malignant cells. The cytotoxic effects are exerted by their biologically active
metabolites, with methylselenol (CH3SeH) being one of the key executors. In search of novel
CH3SeH precursors, we previously synthesized a series of methylselenoesters that were active
(GI50 < 10 µM at 72 h) against a panel of cancer cell lines. Herein, we refined the mechanism of action
of the two lead compounds with the additional synthesis of new analogs (ethyl, pentyl, and benzyl
derivatives). A novel mechanism for the programmed cell death mechanism for Se-compounds
was identified. Both methylseleninic acid and the novel CH3SeH precursors induced entosis by cell
detachment through downregulation of cell division control protein 42 homolog (CDC42) and its
downstream effector β1-integrin (CD29). To our knowledge, this is the first time that Se compounds
have been reported to induce this type of cell death and is of importance in the characterization of
the anticancerogenic properties of these compounds
Design, synthesis and anticancer evaluation of novel Se-NSAID hybrid molecules: Identification of a Se-indomethacin analog as a potential therapeutic for breast cancer
A total of twenty-five novel carboxylic acid, methylester, methylamide or cyano nonsteroidal anti-inflammatory
drug (NSAID) derivatives incorporating Se in the chemical form of selenoester were reported. Twenty Se-NSAID
analogs exhibited an increase in cytotoxic potency compared with parent NSAID scaffolds (aspirin, salicylic acid,
naproxen, indomethacin and ketoprofen). Top five analogs were selected to further study their cytotoxicity in a
larger panel of cancer cells and were also submitted to the DTP program of the NCI’s panel of 60 cancer cell lines.
Compounds 4a and 4d stood out with IC50 values below 10 μM in several cancer cells along with a selectivity
index higher than 5 in breast cancer cells. Remarkably, analog 4d was found to inhibit cell growth notably in two
breast cancer cell lines by inducing apoptosis, and to be metabolized to release the parent NSAID along with the
Se fragment. Taken together, our results show that Se-NSAID analog 4d could be a potential chemotherapeutic
drug for breast cancer
A diphenyldiselenide derivative induces autophagy via JNK in HTB-54 lung cancer cells
Symmetric aromatic diselenides are potential anticancer agents with strong cytotoxic activity. In this study, the in vitro anticancer activities of a novel series of diarylseleno derivatives from the diphenyldiselenide (DPDS) scaffold were evaluated. Most of the compounds exhibited high efficacy for inducing cytotoxicity against different human cancer cell lines. DPDS 2, the compound with the lowest mean GI50 value, induced both caspase-dependent apoptosis and arrest at the G0/G1 phase in acute lymphoblastic leucemia CCRF-CEM cells. Consistent with this, PARP cleavage; enhanced caspase-2, -3, -8 and -9 activity; reduced CDK4 expression and increased levels of p53 were detected in these cells upon DPDS 2 treatment. Mutated p53 expressed in CCRF-CEM cells retains its transactivating activity. Therefore, increased levels of p21CIP1 and BAX proteins were also detected. On the other hand, DPDS 6, the compound with the highest selectivity index for cancer cells, resulted in G2/M cell cycle arrest and caspase-independent cell death in p53 deficient HTB-54 lung cancer cells. Autophagy inhibitors 3-methyladenine, wortmannin and chloroquine inhibited DPDS 6-induced cell death. Consistent with autophagy, increased LC3-II and decreased SQSTM1/p62 levels were detected in HTB-54 cells in response to DPDS 6. Induction of JNK phosphorylation and a reduction in phospho-p38 MAPK were also detected. Moreover, the JNK inhibitor SP600125-protected HTB-54 cells from DPDS 6-induced cell death indicating that JNK activation is involved in DPDS 6-induced autophagy. These results highlight the anticancer effects of these derivatives and warrant future studies examining their clinical potential
Técnicas e instrumentos de evaluación y su incidencia en el rendimiento académico
This research aims to determine the incidence of the use of evaluation techniques and instruments, to improve academic performance in the subject of Social Studies, of the sixth grade of the school of Basic General Education "Filomena Mora de Carrión". It has a quantitative-qualitative research approach, the research design was non-experimental, the type of research used was exploratory and descriptive, the methods that were executed are scientific, inductive, analytical, interpretive and statistical; On the other hand, for the application of techniques such as the survey and the interview of their population and sample, 48 students and two teachers of the institution were selected through a non-probability sampling. The results that stand out most are that the use of appropriate techniques and instruments have a significant impact on academic performance, since students will understand clearly and precisely the topics taught, which is why they must be used effectively; These allow to provide important feedback to students, managing to identify objectives achieved and not achieved, and in turn helps to keep students motivated to continue learning.La presente investigación tiene como objetivo determinar la incidencia del uso de técnicas e instrumentos de evaluación, para mejorar el rendimiento académico en la asignatura de Estudios Sociales, del sexto grado de la escuela de Educación General Básica “Filomena Mora de Carrión”. Posee un enfoque de investigación cuanti-cualitativo, el diseño de la investigación fue no experimental, el tipo de investigación empleado fue exploratorio y descriptivo, los métodos que se ejecutaron son el científico, inductivo, analítico, interpretativo y estadístico; por otro lado, para la aplicación de técnicas como la encuesta y la entrevista su población y muestra, fueron seleccionados mediante un muestreo no probabilístico, 48 estudiantes y dos docentes de la institución. Los resultados que más destacan es que el empleo de técnicas e instrumentos adecuados tienen un impacto significativo en el rendimiento académico, ya que los estudiantes comprenderán de forma clara y precisa los temas impartidos, es por ello, que se las debe usar de forma efectiva; estas permiten proporcionar una retroalimentación importante a los estudiantes, logrando identificar objetivos alcanzados y no alcanzados, y a su vez ayuda a mantener motivados a los estudiantes para que sigan aprendiendo
Novel N,N'-disubstituted selenoureas as potential antioxidant and cytotoxic agents
A series of 30 novel N,N disubstituted selenoureas were synthesized, characterized, and
their antioxidant ability was tested using 2,2-diphenyl-1-picrylhydrazyl (DPPH) and 2,20-azinobis(
3-ethylbenzthiazoline-6-sulfonic acid (ABTS) assays. Additionally, their cytotoxic activity was
tested in vitro in a panel of three different cancer (breast, lung and colon) and two normal cell lines.
Each selenourea entity contains a para-substituted phenyl ring with different electron-withdrawing
and electron-donating groups, and different aliphatic and aromatic nuclei. All of the synthesized
selenoureas present antioxidant capacity at high concentrations in the DPPH assay, and three of them
(2b, 2c and 2d) showed greater radical scavenging capacity than ascorbic acid at lower concentrations.
These results were confirmed by the ABTS assay, where these novel selenoureas present even higher
antioxidant capacity than the reference compound Trolox. On the other hand, 10 selenoureas present
IC50 values below 10 M in at least one cancer cell line, resulting in the adamantyl nucleus (6a¿
6e), the most interesting in terms of activity and selectivity. Outstanding results were found for
selenourea 6c, tested in the NCI60 cell line panel and showing an average GI50 of 1.49 M for the
60 cell lines, and LC50 values ranging from 9.33 M to 4.27 M against 10 of these cancer cell lines.
To gain insight into its anticancer activity mechanism, we investigated the cell cycle progression
of the promising
Effect of topical berberine in murine cutaneous leishmaniasis lesions
Objectives: More effective topical treatments remain an unmet need for the localized forms of cutaneous leishmaniasis (CL). The aim of this study was to evaluate the efficacy and safety of a topical berberine cream in
BALB/c mice infected with Leishmania major parasites.
Methods: A cream containing 0.5% berberine-β-glycerophosphate salt and 2.5% menthol was prepared. Its
physicochemical and stability properties were determined. The cream was evaluated for its capacity to reduce
lesion size and parasitic load as well as to promote wound healing after twice-a-day administration for 35 days.
Clinical biochemical profile was used for estimating off-target effects. In vitro time-to-kill curves in L. major-infected macrophages and skin and plasma pharmacokinetics were determined, aiming to establish pharmacokinetic/pharmacodynamic relationships.
Results: The cream was stable at 40°C for 3 months and at 4°C for at least 8 months. It was able to halt lesion
progression in all treated mice. At the end of treatment, parasite load in the skin was reduced by 99.9% (4 log)
and genes involved in the wound healing process were up-regulated compared with untreated mice.
The observed effects were higher than expected from in vitro time-to-kill kinetic and plasma berberine concentrations, which ranged between 0.07 and 0.22 μM.
Conclusions: The twice-a-day administration of a topical berberine cream was safe, able to stop parasite progression and improved the appearance of skin CL lesions. The relationship between drug plasma levels and in vivo effect was unclear
New symmetrical quinazoline derivatives selectively induce apoptosis in human cancer cells
In the search of new symmetrical derivatives with anticancer activity, we have looked for novel compounds able to induce a selective proapoptotic mechanism in cancer cells. The potential antitumoral activity of several quinazoline derivatives was evaluated in vitro examining their cytotoxic effects against human breast, colon and bladder cancer cell lines. The IC(50) value of the compounds that showed cytotoxic activity was calculated. These compounds were tested for their ability to induce caspase-3 activation and nuclear chromatin degradation. Non-tumoral human cell lines were used to test the selectivity of the cytotoxic compounds against cancer cells. Several compounds showed no cytotoxicity in these cell lines. Finally, JRF12 (2,4-dibenzylaminoquinazoline) was chosen as the best candidate and its mechanism of action was studied in more detail. A time dependent evaluation of apoptosis was performed in the three cancer cell lines, followed by an evaluation of the cell cycle regulation involvement that showed a decrease of cells in G(1) phase and increase of cells in G(2) phase before cell death. 2,4-dibenzylaminoquinazoline treatment produces few changes in the expression of genes as evaluated by using oligonucleotide microarrays and Q-RT-PCR assays. In conclusion, 2,4-dibenzylaminoquinazoline is a promising anticancer drug showing cytostatic and apoptotic effects mainly in a transcription independent manner
In vitro antileishmanial activity and iron superoxide dismutase inhibition of arylamine Mannich base derivatives
Leishmaniasis is one of the world’s most neglected diseases, and it has a worldwide prevalence of 12 million. There are no effective human vaccines for its prevention, and treatment is hampered by outdated drugs. Therefore, research aiming at the development of new therapeutic tools to fight Leishmaniasis remains a crucial goal today. With this purpose in mind, we present twenty arylaminoketone derivatives with a very interesting in vitro and in vivo efficacy against Trypanosoma cruzi that have now been studied against promastigote and amastigote forms of L. infantum, L. donovani and L. braziliensis strains. Six out of the twenty Mannich base-type derivatives showed Selectivity Index between 39 and 2337 times higher in the amastigote form than the reference drug glucantime. These six derivatives affected the parasite infectivity rates; the result was lower parasite infectivity rates than glucantime tested at a IC25 dose. In addition, these derivatives were substantially more active against the three Leishmania species tested than glucantime. The mechanism of action of these compounds has been studied, showing a greater alteration in glucose catabolism and leading to greater levels of Fe-SOD (iron superoxide dismutase) inhibition. These molecules could be potential candidates for Leishmaniasis chemotherapy
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