Seven new abietane diterpenoids, comprising medusanthol A–G (1–3, 5, 7–9) and two previously identified analogs (4 and 6), were isolated from the hexane extract of the aerial parts of Medusantha ...martiusii. The structures of the compounds were elucidated by HRESIMS, 1D/2D NMR spectroscopic data, IR spectroscopy, NMR calculations with DP4+ probability analysis, and ECD calculations. The anti-neuroinflammatory potential of compounds 1–7 was evaluated by determining their ability to inhibit the production of nitric oxide (NO) and the proinflammatory cytokine TNF-α in BV2 microglia stimulated with LPS and IFN-γ. Compounds 1–4 and 7 exhibited decreased NO levels at a concentration of 12.5 µM. Compound 1 demonstrated strong activity with an IC50 of 3.12 µM, and compound 2 had an IC50 of 15.53 µM; both compounds effectively reduced NO levels compared to the positive control quercetin (IC50 11.8 µM). Additionally, both compounds significantly decreased TNF-α levels, indicating their potential as promising anti-neuroinflammatory agents.
Oral squamous cell carcinoma (OSCC) is a worldwide public health problem, accounting for approximately 90% of all oral cancers, and is the eighth most common cancer in men. Cisplatin and carboplatin ...are the main chemotherapy drugs used in the clinic. However, in addition to their serious side effects, such as damage to the nervous system and kidneys, there is also drug resistance. Thus, the development of new drugs becomes of great importance. Naphthoquinones have been described with antitumor activity. Some of them are found in nature, but semi synthesis has been used as strategy to find new chemical entities for the treatment of cancer. In the present study, we promote a multiple component reaction (MCR) among lawsone, arylaldehydes, and benzylamine to produce sixteen chemoselectively derivated Mannich adducts of 1,4-naphthoquinones in good yield (up to 97%). The antitumor activities and molecular mechanisms of action of these compounds were investigated in OSCC models and the compound 6a induced cytotoxicity in three different tumor cell lines (OSCC4, OSCC9, and OSCC25) and was more selective (IS > 2) for tumor cells than the chemotropic drug carboplatin and the controls lapachol and shikonin, which are chemically similar compounds with cytotoxic effects. The 6a selectively and significantly reduced the amount of cell colony growth, was not hemolytic, and tolerable in mice with no serious side effects at a concentration of 100 mg/kg with a LD50 of 150 mg/kg. The new compound is biologically stable with a profile similar to carboplatin. Morphologically, 6a does not induce cell retraction or membrane blebs, but it does induce intense vesicle formation and late emergence of membrane bubbles. Exploring the mechanism of cell death induction, compound 6a does not induce ROS formation, and cell viability was not affected by inhibitors of apoptosis (ZVAD) and necroptosis (necrostatin 1). Autophagy followed by a late apoptosis process appears to be the death-inducing pathway of 6a, as observed by increased viability by the autophagy inhibitor (3-MA) and by the appearance of autophagosomes, later triggering a process of late apoptosis with the presence of caspase 3/7 and DNA fragmentation. Molecular modeling suggests the ability of the compound to bind to topoisomerase I and II and with greater affinity to hPKM2 enzyme than controls, which could explain the mechanism of cell death by autophagy. Finally, the in-silico prediction of drug-relevant properties showed that compound 6a has a good pharmacokinetic profile when compared to carboplatin and doxorubicin. Among the sixteen naphthoquinones tested, compound 6a was the most effective and is highly selective and well tolerated in animals. The induction of cell death in OSCC through autophagy followed by late apoptosis possibly via inhibition of the PKM2 enzyme points to a promising potential of 6a as a new preclinical anticancer candidate.
After mushroom production, the substrate plus the cultivated mycelium represents a byproduct, the so-called “spent mushroom substrate” (SMS). We evaluated different SMS types in fresh form, recently ...taken from the cultivation rooms, for the production of lettuce and arugula in the open field, greenhouse and greenhouse in pot. Three kinds of SMS were used (i - SMS of ABL (Agaricus subrufescens), ii - SMS of POS (Pleurotus ostreatus) and iii - 50% SMS of ABL + 50% SMS of POS) at three doses (1, 2 and 4 kg m−2). For comparison purposes, two commercial soil conditioners, Forth Condicionador® and Visa Fértil Orgânico®, were used. Finally, chicken manure with reference as international organic material was used. A control treatment consisted of a soil plot without any organic material. The application of fresh SMS in the production of LE (lettuce) and AR (arugula) is feasible considering several agronomic parameters evaluated, therefore that in F (field) the superior results were obtained by the ABL dose of 4 kg m−2, in the GR (green house) at a lower dose ABL with 1 kg m−2, POS with 2 kg m−2 and mix with ABL + POS at doses of 2–4 kg m−2, and finally in GR/P (greenhouse pot) it was proved that in a protected environment by rain the combination ABL + POS at dose of 4 kg m−2 is recommended.
•Fresh SMS of Pleurotus and Agaricus were used for arugula and lettuce cultivation.•Three doses of SMS were used (1, 2 and 4 kg m−2).•Production was carried out in the open field, greenhouse and greenhouse in pot.•In field the superior results were obtained by the ABL dose of 4 kg m−2•In greenhouse (GR) and GR in pot the superior results were ABL + POS doses of 4 kg m−2
Exposure to contaminated water during aquatic recreational activities can lead to gastrointestinal diseases. In order to decrease the exposure risk, the fecal indicator bacteria Escherichia coli is ...routinely monitored, which is time-consuming, labor-intensive, and costly. To assist the stakeholders in the daily management of bathing sites, models have been developed to predict the microbiological quality. However, model performances are highly dependent on the quality of the input data which are usually scarce. In our study, we proposed a conceptual framework for optimizing the selection of the most adapted model, and to enrich the training dataset. This frameword was successfully applied to the prediction of Escherichia coli concentrations in the Marne River (Paris Area, France). We compared the performance of six machine learning (ML)-based models: K-nearest neighbors, Decision Tree, Support Vector Machines, Bagging, Random Forest, and Adaptive boosting. Based on several statistical metrics, the Random Forest model presented the best accuracy compared to the other models. However, 53.2 ± 3.5% of the predicted E. coli densities were inaccurately estimated according to the mean absolute percentage error (MAPE). Four parameters (temperature, conductivity, 24 h cumulative rainfall of the previous day the sampling, and the river flow) were identified as key variables to be monitored for optimization of the ML model. The set of values to be optimized will feed an alert system for monitoring the microbiological quality of the water through combined strategy of in situ manual sampling and the deployment of a network of sensors. Based on these results, we propose a guideline for ML model selection and sampling optimization.
Mandevilla Lindl. is an important genus of the Apocynaceae family, not only as ornamental plants but also for its medicinal uses. In Brazil, Mandevilla species are indicated to treat asthma and skin ...infections, their anti-inflammatory potential and wound healing properties are also reported in the literature. Concerning their chemical composition, this group of plants is a conspicuous producer of pregnane glycosides. Mandevilla dardanoi is an endemic species from the Brazilian semiarid region not studied by any phytochemical methods. In view of the medicinal potential of Mandevilla species, this study aimed to isolate new pregnane glycosides from M. dardanoi. To achieve this main goal, modern chromatography techniques were employed. Five new pregnane glycosides, dardanols A-E, were isolated from the roots of M. dardanoi by HPLC. Their structures were determined using extensive 1D and 2D-NMR and mass spectrometry (MSn and HRESIMS) data. The cytotoxicity and the anti-inflammatory potential of these compounds were evaluated. The first was evaluated by measuring proinflammatory cytokines and nitric oxide production by stimulated macrophages. Dardanols were able to inhibit the production of nitric oxide and reduce IL-1β and TNF-α. The current work demonstrates the chemodiversity of Brazilian semiarid species and contributes to amplifying knowledge about the biological potential of the Mandevilla genus.
The use of agrochemicals has become a standard practice worldwide to ensure the productivity and quality of sugarcane crops. This study aimed to analyze the metabolic changes in sugarcane culms ...treated with five different nematicides. The experimental design was randomized in blocks, and agro-industrial and biometric variables were evaluated. The samples were extracted and then analyzed using LC-MS, LC-MS/MS, and LC-HRMS. The data obtained were submitted to statistical methods (PCA and PLS). Fragmentation patterns, retention time, and UV absorptions of the main features were analyzed. The plantations treated with carbosulfan (T4) obtained higher agricultural productivity and total recoverable sugar (TRS), while the use of benfuracarb (T3) was associated with lower growth and lower TRS. Statistical analysis revealed the contribution of the features at
/
353 and
/
515, assigned as chlorogenic acids, which discriminated the groups. The MS profile also supported the occurrence of flavonoids (C-glycosides and O-glycosides) in the samples.
Herein, the isolation of secondary metabolites from the aerial parts of Justicia aequilabris guided by HPLC-MS n and molecular networking analyses is reported. Twenty-two known compounds were ...dereplicated. Three new lignans (aequilabrines A–C (1–3)) and three known compounds (lariciresinol-4′-O-β-glucose (4), roseoside (5), and allantoin (6)) were obtained. The anti-inflammatory activity of compounds 1–3 was evaluated in vitro by inhibiting the nitric oxide production (NO) and pro-inflammatory activity on the cytokine IL-1β. Compounds 2 and 3 showed significant inhibitory activity against NO production, with IC50 values of 9.1 and 7.3 μM, respectively. The maximum inhibition of IL-1β production was 23.5% (1), 27.3% (2), and 32.5% (3).
Monitoring water quality in urban rivers is crucial for water resource management since point and non-point source pollution remain a major challenge. However, traditional water quality monitoring ...methods are costly and limited in frequency and spatial coverage. To optimize the monitoring, techniques such as modeling have been proposed. These methods rely on networks of low-cost multiprobes integrated with IoT networks to offer continuous real-time monitoring, with sufficient spatial coverage. But challenges persist in terms of data quality. Here, we propose a framework to verify the reliability and stability of low-cost sensors, focusing on the implementation of multiparameter probes embedding six sensors. Various tests have been developed to validate these sensors. First of all, a calibration check was carried out, indicating good accuracy. We then analyzed the influence of temperature. This revealed that for the conductivity and the oxygen sensors, a temperature compensation was required, and correction coefficients were identified. Temporal stability was verified in the laboratory and in the field (from 3 h to 3 months), which helped identify the frequency of maintenance procedures. To compensate for the sensor drift, weekly calibration and cleaning were required. This paper also explores the feasibility of LoRa technology for real-time data retrieval. However, with the LoRa gateways tested, the communication distance with the sensing device did not exceed 200 m. Based on these results, we propose a validation method to verify and to assure the performance of the low-cost sensors for water quality monitoring.
Natural products have played a pivotal role for the discovery of anticancer drugs. Tonantzitlolones are flexibilan-type diterpenes rare in nature; therefore, few reports have shown antiviral and ...cytotoxic activities. This study aimed to investigate the in vivo antitumor action of Tonantzitlolone B (TNZ-B) and its toxicity. Toxicity was evaluated in mice (acute and micronucleus assays). Antitumor activity of TNZ-B (1.5 or 3 mg/kg intraperitoneally — i.p.) was assessed in Ehrlich ascites carcinoma model. Angiogenesis and reactive oxygen species (ROS) and nitric oxide (NO) production were also investigated, in addition to toxicological effects after 7-day treatment. The LD
50
(lethal dose 50%) was estimated at around 25 mg/kg (i.p.), and no genotoxicity was recorded. TNZ-B reduced the Ehrlich tumor’s volume and total viable cancer cell count (
p
< 0.001 for both). Additionally, TNZ-B reduced peritumoral microvessel density (
p
< 0.01), suggesting antiangiogenic action. Moreover, a decrease was observed on ROS (
p
< 0.05) and nitric oxide (
p
< 0.001) levels. No significant clinical findings were observed in the analysis of biochemical, hematological, and histological (liver and kidney) parameters. In conclusion, TNZ-B exerts antitumor and antiangiogenic effects by reducing ROS and NO levels and has weak in vivo dose-repeated toxicity. These data contribute to elucidate the antitumor action of TNZ-B and point the way for further studies with this natural compound as an anticancer drug.
ENT-ABIETANE DITERPENES FROM Euphorbia phosphorea (EUPHORBIACEAE). Phytochemical study of the roots of Euphorbia phosphorea Mart. (Euphorbiaceae) was carried out through chromatographic techniques, ...resulting in the isolation of a new ent-abietane diterpene named 11β,12β-dihydroxy-ent-abieta-8(14),13(15)-dien-16,12α-olide (1), and of nine known ent-abietane diterpenes jolkinolide A (2), jolkinolide E (3), euphorin H (4), euphopilolide (5) jolkinolide F (6), ent-12-hydroxy-12R-abieta8(14),13(15)-dien-16,12-olide (7), ent-11α-hydroxyabieta-8(14),13(15)-dien-16,12α-olide (8), 17-hydroxyjolkinolide B (9) and caudicifolin (10). The structures of all compounds were established using spectroscopic techniques such as 1D and 2D NMR, and the structure of the compound 1 was established also with MS, IR and ECD. All compounds were submitted to an in silico study through of a predictive model and then submitted to in vitro tests against Mycobacterium tuberculosis and M. smegmatis for evaluation of their antimycobacterial activity. Compounds 5 and 9 showed mycobacterial growth inhibition with MIC values of 62.5 μM against M. tuberculosis and M. smegmatis, respectively.