•Two synthetic alkaloids were cytotoxic against tumor cell lines.•Alkaloid 3-APA 2 presented high selectivity against breast and ovary cancer cells.•Compounds assessed induced genotoxic and mutagenic ...effects.•Genotoxicity and mutagenicity were more pronounced in cancer cells.•Metabolic activation enhanced the toxic effects.
The pharmacological potential of drugs must be evaluated to establish their potential therapeutic benefits and side effects. This evaluation includes assessment of the effects of hepatic enzymes that catalyse their metabolic activation. Previously, our research group synthesized and characterized a set of synthetic 3-alkyl pyridine alkaloid (3-APA) analogues that cause in vitro cytotoxic, genotoxic, and mutagenic effects in various human cancer cell lines. The present study aimed to evaluate these activities with the two most promising synthetic 3-APAs (3-APA 1 and 3-APA 2) against cell lines derived from breast cancer (MDA-MB-231), ovarian cancer (TOV-21 G) and lung fibroblasts (WI-26-VA4) with and without metabolic activation (S9 fraction). The cytotoxicity of the compounds was evaluated employing MTT and clonogenic assays. In addition, comet assays, γH2AX immunocytochemistry labelling assays and cytokinesis-block micronucleus tests were carried out to evaluate the potential of these compounds to induce chromosomal damage. The results obtained in the MTT assay showed that compound 3-APA 2 exhibited high selectivity index (SI) values (ranging between 21.0 and 92.6). In addition, the cytotoxicity of the compounds was clearly enhanced by metabolic activation. Moreover, both compounds were genotoxic and induced double-strand breaks in DNA and chromosomal lesions with and without S9. The cancer cell lines tested showed higher genotoxic sensitivity to the compounds than did the non-tumour cell line used as a reference. The genotoxic and mutagenic effects of the compounds were potentiated in experiments with metabolic activation. The data obtained in this study indicate that compound 3-APA 2 is more active against the human cancer cell lines tested, both with and without metabolic activation, and can therefore be considered a candidate drug to treat human ovarian and breast cancer.
The Amazon biome is influenced by El Niño event, which reduce precipitation and increase temperature. However, little is known about its effects on tree formation dynamics in this region. Here, we ...evaluated the effects of local (precipitation, temperature, and solar insolation) and large-scale (El Niño) climatic variables on wood traits of Tectona grandis (teak) in the Amazon. Discs were collected from the base of trees aged 12 years and used for anatomical and physical analyses. We evaluated three periods (i.e., pre-El Niño (2012/2013), El Niño (2014/2015), and post-El Niño (2016/2017)). Wood density, vessels, and rays were compared to local and large-scale climatic variables. The extreme drought caused by El Niño event reduced the width and length of teak vessels. Additionally, precipitation during some months of the year increased vessel size and wood density. In some months of the year, ambient temperature reduced vessel width and length. Moreover, the effect of solar insolation depended on soil moisture availability. Thus, our results provided clear evidence of teak acclimatization to El Niño in the Amazon region and should promote further studies on tree responses to climate.
Cancer of the head and neck is a group of upper aerodigestive tract neoplasms in which aggressive treatments may cause harmful side effects to the patient. In the last decade, investigations on ...natural compounds have been particularly successful in the field of anticancer drug research. Our aim is to evaluate the antitumor effect of
Aubl. extracts on a panel of head and neck squamous cell carcinoma (HNSCC) cell lines. Analysis of secondary metabolites classes in fractions of
was performed using Nuclear Magnetic Resonance (NMR). Mutagenicity effect was evaluated by Ames mutagenicity assay. The cytotoxic effect, and migration and invasion inhibition were measured. Additionally, the expression level of apoptosis-related molecules (PARP, Caspases 3, and Fas) and MMP-2 was detected using Western blot. Heterogeneous cytotoxicity response was observed for all fractions, which showed migration inhibition, reduced matrix degradation, and decreased cell invasion ability. Expression levels of MMP-2 decreased in all fractions, and particularly in the hexane fraction. Furthermore, overexpression of FAS and caspase-3, and increase of cleaved PARP indicates possible apoptosis extrinsic pathway activation. Antiproliferative activity of
extract in HNSCC cells lines suggests the possibility of developing an anticancer agent or an additive with synergic activities associated with conventional anticancer therapy.
Digoxin is a drug widely used to treat heart failure and studies have demonstrated its potential as anticancer agent. In addition, digoxin presents the potential to interact with a series of other ...compounds used in medicine. The aim of the present study was to evaluate in vitro the cytotoxicity, genotoxicity and mutagenicity of digoxin and its potential to interact with the mutagen Mitomycin C (MMC). The cytotoxicity of digoxin was assessed by employing the MTT method and the comet assay was performed to assess the genotoxicity of this medicine in CHO-K1 and HeLa cell lines. Besides, the cytokinesis-block micronucleus assay was performed to assess the mutagenicity and the antimutagenicity of this drug. The Ames assay was also performed with TA98 and TA100 strains of
S. typhimurium
. Results showed that digoxin was cytotoxic, genotoxic and mutagenic for HeLa and CHO-K1 cell lines at concentrations many times higher than those observed in human therapeutic conditions. Nevertheless, an antimutagenic effect against the mutagen MMC was observed on both cell lines in concentrations near those used therapeutically in humans. This chemoprotective effect observed is an interesting finding that should be better explored regarding its impact in anticancer chemotherapy.
The present work is focussed on the principles of photodynamic therapy (PDT), emphasizing the photochemical mechanisms of reactive oxygen species formation and the consequent biochemical processes ...generated by the action of reactive oxygen species on various biological macromolecules and organelles. This paper also presents some of the most used photosensitizers, including Photofrin, and the new prototypes of photosensitizers, analysing their physicochemical and spectroscopic properties. At this point, the review discusses the therapeutic window of absorption of specific wavelengths involving first- and second-generation photosensitizers, as well as the principal light sources used in PDT. Additionally, the aggregation process, which consists in a phenomenon common to several photosensitizers, is studied. J-aggregates and H-aggregates are discussed, along with their spectroscopic effects. Most photosensitizers have a significant hydrophobic character; thus, the study of the types of aggregation in aqueous solvent is very relevant. Important aspects of the coordination chemistry of metalloporphyrins and metallophthalocyanines used as photosensitizers are also discussed. The state-of-the-art in PDT is evaluated, discussing recent articles in this area. Furthermore, macrocyclic photosensitizers, such as porphyrins and phthalocyanines, are specifically described. The present review is an important contribution, because PDT is one of the most auspicious advances in the therapy against cancer and other non-malignant diseases.
The practice of physical exercise, especially resistance exercise, is important for the treatment and/or prevention of cardiovascular risk factors in adult individuals. However, there are few studies ...on its effects on adolescent individuals. Therefore, the aim of the present study was to evaluate the effects of applying a 12-week resistance training program on cardiovascular risk factors in adolescents.
Thus, 122 adolescents aged 13-16 years of both genders participated in the study from school in the city of Lagarto, Sergipe (SE), Brazil, divided into two groups: Control Group (CG) and Group undergoing resistance training (RTG). Blood collection and anthropometric measurements were performed before and after the 12-week resistance training program (RTP).
After 12 weeks of the RTP in the adolescents, there was a reduction in the triglyceride variables (9.55%,
= 0.0286), Low-Density Lipoproteins (LDL) (5.42%,
= 0.0244), non-High-Density Lipoproteins (HDL) (5.40%,
= 0.0019), blood glucose (6.71%,
= 0.0040), systolic blood pressure (10.13%,
< 0.0001), as well as an increase in the body weight variable (1.73%,
= 0.0003).
It was concluded that a 12-week RTP can prevent and/or alleviate the development of several chronic degenerative diseases in adulthood and that resistance training is important for maintaining the health of adolescents.
Objective The aim of the study was to compare the thickness of primary tumors with the frequency of nodal metastases and survival in patients surgically treated for T1/T2N0 oral tongue squamous cell ...carcinoma. Study Design This is a retrospective longitudinal study with 74 patients. Results None of the patients with a tumor thickness (TT) ≤ 7 mm presented with nodal metastasis, whereas 25 of the patients with a TT > 7 mm (51.0%) developed metastases ( P < .0001). Multivariate analysis showed that TT > 7 mm was a risk factor for occult nodal metastasis (odds ratio = 8.7; P = .002) with 81.9% accuracy. TT > 10 mm was also a predictive factor of worse disease-free survival in these patients (hazard ratio = 12.2; P = .003). Conclusions Tumor thickness of greater than 7 mm is predictive of a higher incidence of lymph node metastasis, and a TT > 10 mm is predictive of worse disease-free survival in squamous cell carcinoma of the oral tongue.
Although the presence of nitro groups in chemicals can be recognized as structural alerts for mutagenicity and carcinogenicity, nitroaromatic compounds have attracted considerable interest as a class ...of agents that can serve as source of potential new anticancer agents. In the present study, the in vitro cytotoxicity, genotoxicity, and mutagenicity of three synthetic ortho-nitrobenzyl derivatives (named ON-1, ON-2 and ON-3) were evaluated by employing human breast and ovarian cancer cell lines. A series of biological assays was carried out with and without metabolic activation. Complementarily, computational predictions of the pharmacokinetic properties and druglikeness of the compounds were performed in the Swiss ADME platform. The MTT assay showed that the compounds selectively affected selectively the cell viability of cancer cells in comparison with a nontumoral cell line. Additionally, the metabolic activation enhanced cytotoxicity, and the compounds affected cell survival, as demonstrated by the clonogenic assay. The comet assay, the cytokinesis-block micronucleus assay, and the immunofluorescence of the γ-H2AX foci formation assay have that the compounds caused chromosomal damage to the cancer cells, with and without metabolic activation. The results obtained in the present study showed that the compounds assessed were genotoxic and mutagenic, inducing double-strand breaks in the DNA structure. The high selectivity indices observed for the compounds ON-2 and ON-3, especially after metabolic activation with the S9 fraction, must be highlighted. These experimental biological results, as well as the theoretical properties predicted for the compounds have shown that they are promising anticancer candidates to be exploited in additional studies.
A series of 16 simple long-chain alkyltriazoles and two novel alkylphosphocholine derivatives containing an azide moiety were evaluated in vitro for their leishmanicidal activity against. Among the ...18 compounds tested, the eight most active compounds against promastigote forms were selected for further evaluation against amastigote forms. These compounds were also evaluated for their cytotoxicity against murine macrophages and tested as inhibitors of cysteine protease rCPB2.8, an important target for development of antileishmanial drugs. The mutagenicity of some of these compounds was also evaluated in prokaryotic and eukaryotic cells to assess any genetic effects of the leishmanicidal candidates. The compound 4, an alkylphosphocholine derivative, was found to be the most potent against amastigote forms with an IC50 of 3.81 μM, comparable to that of pentamidine (IC50 = 6.62 μM) and amphotericin B (IC50 = 6.10 μM), two established leishmanicidal drugs. Compound 4 also exhibited the best selectivity index (SI) values of the series, demonstrating low toxicity against macrophages and a cLogP value higher than 5. Among the alkyltriazoles, compounds 13 and 14 were the most active against promastigote and amastigote forms. They were then evaluated for their mutagenicity in vitro; the mutagenicity index (MI) values were lower than 2, suggesting that these compounds are not mutagenic.
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•Novel alkylphosphocholine and alkyltriazole compounds were synthesized.•The compounds were tested in vitro against Leishmania amazonensis.•The cytotoxicity and mutagenicity of most active compounds were tested.•The most active compounds were tested as inhibitors of cysteine protease rCPB2.8.•The alkyltriazoles may be a promising template for developing leishmanicidal agents.
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