Graphitic carbon nitride as a novel anticancer agent: potential mechanisms and efficacy in prostate cancer and glioblastoma treatment.

Carbon-derived compounds are gaining traction in the scientific community because of their unique properties, such as conductivity and strength, and promising innovations in technology and medicine. Graphitic nitride carbon (g-C3N4) stands out among these compounds because of its potential in antitumor therapies. This study aimed to assess g-C3N4's antitumor potential and cytotoxic mechanisms. Prostate cancer (DU-145) and glioblastoma (U87) cell lines were used to evaluate antitumor effects, whereas RAW 264.7 and HFF-1 non-tumor cells were used for selectivity evaluation. The synthesized g-C3N4 particles underwent comprehensive characterization, including the assessment of particle size, morphology, and oxygen content, employing various techniques, such as X-ray diffraction, X-ray photoelectron spectroscopy, scanning electron microscopy, energy dispersive X-ray spectroscopy, transmission electron microscopy, and atomic force microscopy. The results indicated that g-C3N4 significantly affected tumor cell proliferation and viability, exhibiting high cytotoxicity within 48 h. In non-tumor cells, minimal effects on proliferation were observed, except for damage to the cell membranes of RAW 264.7 cells. Moreover, g-C3N4 changed the cell morphology and ultrastructure, affecting cell migration in U87 cells and potentially enhancing migration in RAW 264.7 cells. Biochemical assays in Balb/C mice revealed alterations in alanine aminotransferase, aspartate aminotransferase, and amylase levels. In conclusion, g-C3N4 demonstrated promising antitumor effects with minimal toxicity to non-tumor cells, suggesting its potential in neoplasm treatment.

Silver Nanoparticle-Embedded Carbon Nitride: Antifungal Activity on Candida albicans and Toxicity toward Animal Cells.

The development of engineered nanomaterials has been considered a promising strategy to control oral infections. In this study, silver-embedded carbon nitrides (Ag@g-CN) were synthesized and tested against Candida albicans, investigating their antifungal action and biocompatibility in animal cells. Ag@g-CN was synthesized by a simple one-pot thermal polymerization technique and characterized by various analytical techniques. X-ray diffraction (XRD) analysis revealed slight alterations in the crystal structure of g-CN upon the incorporation of Ag. Fourier transform infrared (FT-IR) spectroscopy confirmed the presence of Ag-N bonds, indicating successful silver incorporation and potential interactions with g-CN's amino groups. UV-vis spectroscopy demonstrated a red shift in the absorption edge of Ag@g-CN compared with g-CN, attributed to the surface plasmon resonance effect of silver nanoparticles. Field emission scanning electron microscopy (FE-SEM) and transmission electron microscopy (TEM) confirmed the 2D layered sheet like morphology of both materials. The Ag 3d peaks found in X-ray photoelectron spectroscopy (XPS) confirmed the presence of metallic Ag0 nanoparticles in Ag@g-CN. The Ag@g-CN materials exhibited high antifungal activity against reference and oral clinical strains of C. albicans, with minimal inhibitory concentration (MIC) ranges between 16-256 µg/mL. The mechanism of Ag@g-CN on C. albicans was attributed to the disruption of the membrane integrity and disturbance of the biofilm. In addition, the Ag@g-CN material showed good biocompatibility in the fibroblastic cell line and in Galleria mellonella, with no apparent cytotoxicity observed at a concentration up to 1000 µg/mL. These findings demonstrate the potential of the Ag@g-CN material as an effective and safe antifungal agent for the treatment of oral fungal infections.

Design, synthesis and antibacterial evaluation of ocotillol derivatives with polycyclic nitrogen-containing groups.

Aim: With the increasing abuse of antibacterial drugs, multidrug-resistant bacteria have become a burden on human health and the healthcare system. To find alternative compounds effective against hospital-acquired methicillin-resistant Staphylococcus aureus (HA-MRSA), novel derivatives of ocotillol were synthesized. Methods & Results: Ocotillol derivatives with polycyclic nitrogen-containing groups were synthesized and evaluated for in vitro antibacterial activity. Compounds 36-39 exhibited potent antibacterial activity against HA-MRSA, with MIC = 8-64 µg/ml. Additionally, a combination of compound 37 and the commercially available antibiotic kanamycin showed synergistic inhibitory effects, with a fractional inhibitory concentration index of ≤0.375. Conclusion: Compound 37 has a strong inhibitory effect, and this derivative has potential for use as a pharmacological tool to explore antibacterial mechanisms.

Polyamines and Related Nitrogen Compounds in the Chemotherapy of Neglected Diseases Caused by Kinetoplastids.

Neglected diseases due to the parasitic protozoa Leishmania and Trypanosoma (kinetoplastids) affect millions of people worldwide, and the lack of suitable treatments has promoted an ongoing drug discovery effort to identify novel nontoxic and cost-effective chemotherapies. Polyamines are ubiquitous small organic molecules that play key roles in kinetoplastid parasites metabolism, redox homeostasis and in the normal progression of cell cycles, which differ from those found in the mammalian host. These features make polyamines attractive in terms of antiparasitic drug development. The present work provides a comprehensive insight on the use of polyamine derivatives and related nitrogen compounds in the chemotherapy of kinetoplastid diseases. The amount of literature on this subject is considerable, and a classification considering drug targets and chemical structures were made. Polyamines, aminoalcohols and basic heterocycles designed to target the relevant parasitic enzyme trypanothione reductase are discussed in the first section, followed by compounds directed to less common targets, like parasite SOD and the aminopurine P2 transporter. Finally, the third section comprises nitrogen compounds structurally derived from antimalaric agents. References on the chemical synthesis of the selected compounds are reported together with their in vivo and/or in vitro IC50 values, and structureactivity relationships within each group are analyzed. Some favourable structural features were identified from the SAR analyses comprising protonable sites, hydrophobic groups and optimum distances between them. The importance of certain pharmacophoric groups or amino acid residues in the bioactivity of polyamine derived compounds is also discussed.

ESR, electrochemical, molecular modeling and biological evaluation of 4-substituted and 1,4-disubstituted 7-nitroquinoxalin-2-ones as potential anti-Trypanosoma cruzi agents.

Electrochemical and ESR studies were carried out in this work with the aim of characterizing the reduction mechanisms of 4-substituted and 1,4-disubstituted 7-nitroquinoxalin-2-ones by means of cyclic voltammetry in DMSO as aprotic solvent. Two reduction mechanisms were found for these compounds: the first, for compounds bearing a labile hydrogen by following a self-protonation mechanism (ECE steps), and the second, for compounds without labile hydrogen, based on a purely electrochemical reduction mechanism (typical of nitroheterocycles). The electrochemical results were corroborated using ESR spectroscopy allowing us to propose the hyperfine splitting pattern of the nitro-radical, which was later corroborated by the ESR simulation spectra. All these compounds were assayed as growth inhibitors against Trypanosoma cruzi: first, on the non-proliferative (and infective) form of the parasite (trypomastigote stage), and then, the ones that displayed activity, were assayed on the non-infective form (epimastigote stage). Thus, we found four new compounds highly active against T. cruzi. Finally, molecular modeling studies suggest the inhibition of the trypanothione reductase like one of the possible mechanisms involved in the trypanocidal action.

QSAR study and molecular design of open-chain enaminones as anticonvulsant agents.

Present work employs the QSAR formalism to predict the ED(50) anticonvulsant activity of ringed-enaminones, in order to apply these relationships for the prediction of unknown open-chain compounds containing the same types of functional groups in their molecular structure. Two different modeling approaches are applied with the purpose of comparing the consistency of our results: (a) the search of molecular descriptors via multivariable linear regressions; and (b) the calculation of flexible descriptors with the CORAL (CORrelation And Logic) program. Among the results found, we propose some potent candidate open-chain enaminones having ED(50) values lower than 10 mg·kg(-1) for corresponding pharmacological studies. These compounds are classified as Class 1 and Class 2 according to the Anticonvulsant Selection Project.

Intake and digestibility in cattle fed low-quality tropical forage and supplemented with nitrogenous compounds.

The effects of supplementation with nitrogenous compounds on intake, digestibility, and microbial protein synthesis in cattle fed low-quality tropical forage were assessed. Five rumen fistulated crossbred Holstein x Gir heifers were used, with initial average live weight of 180 +/- 21 kg. Signal grass (Brachiaria decumbens) hay (48.6 g kg(-1) of crude protein (CP), on a dry matter (DM) basis) was used as roughage. Five treatments were defined according to nitrogen supplementation level (0, 20, 40, 60, and 80 g of CP kg(-1) above the CP level of the hay). A mixture of urea, ammonium sulfate, and albumin at the ratios of 4.5:0.5:1.0, respectively, was used as nitrogen source. The experiment consisted of five experimental periods, according to a 5 x 5 Latin square design. The average CP contents in the diets were 51.9, 71.1, 86.0, 116.7, and 130.2 g kg(-1), on a DM basis. A quadratic effect was detected (P < 0.10) of the CP levels in the diets on DM and neutral detergent fiber intake (kg/day), with maximum response at the levels of 102.4 and 100.5 g CP kg(-1) DM, respectively. The average daily concentration of rumen ammonia nitrogen showed increasing linear pattern (P < 0.01) as function of CP levels in the diet, with estimated value of 9.64 mg dL(-1) equivalent to the maximum DM intake. Microbial nitrogen flow in the intestine was linearly and positively related (P < 0.01) with the CP levels in the diet.

A comparative proteomic analysis of Gluconacetobacter diazotrophicus PAL5 at exponential and stationary phases of cultures in the presence of high and low levels of inorganic nitrogen compound.

A proteomic view of G. diazotrophicus PAL5 at the exponential (E) and stationary phases (S) of cultures in the presence of low (L) and high levels (H) of combined nitrogen is presented. The proteomes analyzed on 2D-gels showed 131 proteins (42E+32S+29H+28L) differentially expressed by G. diazotrophicus, from which 46 were identified by combining mass spectrometry and bioinformatics tools. Proteins related to cofactor, energy and DNA metabolisms and cytoplasmic pH homeostasis were differentially expressed in E growth phase, under L and H conditions, in line with the high metabolic rate of the cells and the low pH of the media. Proteins most abundant in S-phase cells were stress associated and transporters plus transferases in agreement with the general phenomenon that binding protein-dependent systems are induced under nutrient limitation as part of hunger response. Cells grown in L condition produced nitrogen-fixation accessory proteins with roles in biosynthesis and stabilization of the nitrogenase complex plus proteins for protection of the nitrogenases from O(2)-induced inactivation. Proteins of the cell wall biogenesis apparatus were also expressed under nitrogen limitation and might function in the reshaping of the nitrogen-fixing G. diazotrophicus cells previously described. Genes whose protein products were detected in our analysis were mapped onto the chromosome and, based on the tendency of functionally related bacterial genes to cluster, we identified genes of particular pathways that could be organized in operons and are co-regulated. These results showed the great potential of proteomics to describe events in G. diazotrophicus cells by looking at proteins expressed under distinct growth conditions.

Toxicidad aguda de un extracto acuoso de Boldoa purpurascens Cav en el modelo de sube y baja en ratas / Acute toxicity of an aqueous extract of Boldoa purpurascens Cav in the up and down model in rats

Fundamentos: Boldoa purpurascens Cav (nitro blanco) ha sido utilizada tradicionalmente como diurética en Cuba, sin embargo, no cuenta con los estudios toxicológicos preclínicos establecidos. Objetivos: determinar la toxicidad aguda de un extracto acuoso liofilizado de hojas secas de B. purpurascens. Métodos: se realizó un estudio preclínico mediante el método de sube y baja (UDP), el grupo experimental estuvo conformado por 5 ratas hembras de la línea Sprague Dawley. Se administró una dosis límite diaria de 2 000 mg/kg. Se realizaron observaciones sistemáticas durante el transcurso del experimento y el día 14 posadministración se procedió a la eutanasia de los animales. Resultados: el peso corporal se comportó acorde a la curva de crecimiento de la especie, sin evidencia de signos tóxicos ni muerte de ningún animal. El estudio anatomopatológico macroscópico de los órganos no mostró alteraciones. Conclusiones: la dosis tóxica del extracto estudiado es superior a 2 000 mg/kg y clasifica como no tóxico(AU)

Foundations: Boldoa purpurascens Cav (nitro blanco) has been traditionally used as a diuretic in Cuba; however, the established preclinical toxicological studies have not been conducted yet. Objectives: to determine acute toxicity in a freeze-dried aqueous extract form dry leaves of B. Purpurascens. Methods: a preclinical study was undertaken by the up and down procedure. The experimental group was composed of 5 Sprague Dawley female rats. A daily limited dose of 2 000 mg/kg was administered. Systematic observations were made during the experiment and on the 14th postadministration day, the euthanasia of the animals was performed. Results: the body weight behaved according to the growth curve of the species without evidence of toxic signs or death of any animal. The macroscopic anatomopathological study of the organs showed no alterations. Conclusions: the toxic dose of the studied extract is higher than 2 000 mg/kg and classifies as non-toxic(AU)

Toxicidad aguda de un extracto acuoso de Boldoa purpurascens Cav en el modelo de sube y baja en ratas / Acute toxicity of an aqueous extract of Boldoa purpurascens Cav in the up and down model in rats

Fundamentos: Boldoa purpurascens Cav (nitro blanco) ha sido utilizada tradicionalmente como diurética en Cuba, sin embargo, no cuenta con los estudios toxicológicos preclínicos establecidos. Objetivos: determinar la toxicidad aguda de un extracto acuoso liofilizado de hojas secas de B. purpurascens. Métodos: se realizó un estudio preclínico mediante el método de sube y baja (UDP), el grupo experimental estuvo conformado por 5 ratas hembras de la línea Sprague Dawley. Se administró una dosis límite diaria de 2 000 mg/kg. Se realizaron observaciones sistemáticas durante el transcurso del experimento y el día 14 posadministración se procedió a la eutanasia de los animales. Resultados: el peso corporal se comportó acorde a la curva de crecimiento de la especie, sin evidencia de signos tóxicos ni muerte de ningún animal. El estudio anatomopatológico macroscópico de los órganos no mostró alteraciones. Conclusiones: la dosis tóxica del extracto estudiado es superior a 2 000 mg/kg y clasifica como no tóxico.

Foundations: Boldoa purpurascens Cav (nitro blanco) has been traditionally used as a diuretic in Cuba; however, the established preclinical toxicological studies have not been conducted yet. Objectives: to determine acute toxicity in a freeze-dried aqueous extract form dry leaves of B. Purpurascens. Methods: a preclinical study was undertaken by the up and down procedure. The experimental group was composed of 5 Sprague Dawley female rats. A daily limited dose of 2 000 mg/kg was administered. Systematic observations were made during the experiment and on the 14th postadministration day, the euthanasia of the animals was performed. Results: the body weight behaved according to the growth curve of the species without evidence of toxic signs or death of any animal. The macroscopic anatomopathological study of the organs showed no alterations. Conclusions: the toxic dose of the studied extract is higher than 2 000 mg/kg and classifies as non-toxic.