Search Results (522)

We report the synthesis, spectroscopic characterization, and single-crystal X-ray structures of 5-methyl-3-phenylbenzo[e][1,2,4]triazine (I) and its precursor N′-(3-methyl-2-nitrophenyl)benzohydrazide (IV). Compound IV was obtained by nucleophilic aromatic substitution of 1-fluoro-3-methyl-2-nitrobenzene with benzohydrazide and was converted to I through a reductive cyclodehydration/oxidative aromatization sequence. The present study provides a concise route to the 5-methyl regioisomer together with full structural characterization and examines how methyl substitution at the 5-position influences molecular geometry and crystal packing relative to the previously reported 6- and 8-methyl analogs. X-ray analysis shows that IV adopts a conjugated hydrazide framework with a twisted N–N linkage and an out-of-plane nitro group. In the crystal, it forms one-dimensional N–H⋯O hydrogen-bonded chains further assembled by weaker intermolecular contacts. By contrast, I displays an essentially planar benzo[e][1,2,4]triazine core with an almost coplanar phenyl substituent and packs into slipped π-stacked columns reinforced by secondary C–H⋯N contacts. Comparison with the previously reported methyl regioisomers shows that relocation of the methyl group to the 5-position has little effect on the intrinsic molecular geometry of the benzo[e][1,2,4]triazine scaffold, while subtly modulating the stacking arrangement and secondary packing interactions in the solid state. These results further define the role of methyl-substituent position in shaping the supramolecular organization of 3-phenylbenzo[e][1,2,4]triazines. Full article

Chalcones are compounds containing an α,β-unsaturated carbonyl group that have been studied due to their structural simplicity, ease of synthesis, and broad spectrum of biological activities. Within this family, nitrochalcones have gained relevance due to the influence of the nitro group (–NO₂) on the modulation of their electronic properties, chemical reactivity, and pharmacological behavior. This review presents a critical analysis of advances in the biological activities and possible mechanisms of action of nitrochalcones and their derivatives, with an emphasis on their structure–activity relationships and therapeutic potential. The available evidence shows that nitrochalcones and their derivatives act as multitarget molecules, capable of intervening in key biological processes such as oxidative stress, mitochondrial dysfunction, inflammation, and cell signaling pathways associated with proliferation and apoptosis. Several studies report anticancer, anti-inflammatory, antiparasitic, antimicrobial, antifungal, and cardiovascular activities, often with favorable selectivity toward pathological cells over healthy cells. Full article

Metabolomic studies in COPD reveal systemic metabolic perturbations, yet sex is often treated as a covariate rather than a biological driver. We aimed to identify plasma metabolites differentiating COPD from controls and to define sex-specific metabolic signatures in both groups. Methods: In this controlled observational study (BIOMEPOC cohort), untargeted plasma metabolomics was performed by LC-MS/MS. Differential abundance was tested across four contrasts (COPD vs. controls; men vs. women within controls; men vs. women within COPD; sex-by-disease interaction) with a false discovery rate (FDR) correction. Because smoking history differed between COPD and controls, a post hoc ever-smokers analysis was conducted. Results: COPD differed from controls in nine metabolites (all decreased): DL-stachydrine, 3-methyl-L-histidine, fructose, pipecolinic and nipecotic acids, 5-nitro-o-toluidine, conjugated linoleic acid, aminoadipate, and creatinine. This pattern is compatible with metabolic depletion, remodeling, and/or altered flux across multiple compartments rather than simple substrate deficiency, spanning muscle-related pools, amino acid handling, carbohydrate-associated metabolism, and exposome-linked inputs. In ever-smokers, results were directionally consistent, with five metabolites remaining nominally significant. Among controls, five metabolites were higher in men after FDR correction (PABA, cis-4-hydroxy-D-proline, N-acetylasparagine, deoxycarnitine, and creatinine), consistent with physiological sex dimorphism in energy pathways, connective-tissue remodeling, and diet/microbiome-related metabolism. Within COPD, six metabolites differed by sex after FDR correction, defining three axes: creatine energy buffering (men: higher GAA/creatinine, lower creatine), purine/urate handling (men: higher urate), and conjugated bile acids (men: higher GCDCA), implicating muscle bioenergetics, redox/inflammatory tone, and gut–liver crosstalk. Conclusions: Plasma metabolomics identifies a pattern compatible with systemic remodeling in COPD and sex-associated divergences in creatine, purine/urate, and bile-acid pathways, supporting a sex-influenced view of systemic COPD heterogeneity and highlighting targets for mechanistic validation. Full article

Translocator protein (TSPO) regulates mitochondrial function, inflammation, and oxidative stress; however, its role in acute myocardial injury (MI) remains incompletely understood. While previous studies have examined TSPO ligands in cardiac injury, the interplay between TSPO modulation and nitric oxide (NO) signaling in AMI has not been systematically investigated. The aim of this study was to investigate the effects of TSPO modulation by PK11195, alone or in combination with nitric oxide synthase (NOS) inhibition by Nω-Nitro-L-arginine methyl ester hydrochloride (L-NAME), on cardiometabolic, inflammatory, oxidative stress, and histopathological parameters in an experimental model of isoprenaline-induced MI in rats. Male Wistar albino rats were divided into four groups: control (C); isoprenaline + saline-treated (ISO); isoprenaline + PK11195-treated (IP); and isoprenaline + PK11195 + L-NAME-treated (IPLN) groups. Isoprenaline administration induced MI, evidenced by elevated cardiac biomarkers, electrocardiographic (ECG) alterations, and histopathological damage. PK11195 treatment significantly attenuated MI and reduced pro-inflammatory cytokine levels while increasing anti-inflammatory cytokine levels, indicating protective effects. Nevertheless, TSPO modulation was associated with adverse metabolic effects, notably elevated fibrinogen and plasma homocysteine levels. Co-administration of L-NAME mechanistically demonstrated that NO availability is essential for PK11195 cardioprotective effects, as NOS inhibition partially abolished cardioprotection and modified oxidative stress parameters. Overall, TSPO modulation exerts complex actions in acute MI through regulating mitochondrial function, inflammatory signaling, and NO pathways, suggesting that TSPO is a potential, multifaceted therapeutic target. Full article

Rubber sealing materials’ aging behavior under challenging circumstances, such as high temperatures, oxygen exposure, or oil immersion, significantly effects how well they seal and how long they last. In order to systematically examine nitrile rubber’s aging behavior and the evolution of mechanical properties under thermo–oxidative and thermo-oil conditions, this study used accelerated high-temperature aging tests. Test results indicate that in a hot-oil environment, the rubber exhibits significant swelling, with mass increasing by up to 9.96%. Hardness undergoes a non-monotonic change, first decreasing and then increasing. In contrast, under thermal-oxidative conditions, hardness increases continuously, exhibiting a marked rise after 7 days of aging at 125 °C. Mechanical property tests revealed a substantial increase in elastic modulus after thermal–oxygen aging. At 125 °C, the modulus rose from an initial 0.4128 MPa to 0.9626 MPa, representing an approximate 133% increase. The compression set reached 83.23% after 7 days of thermal–oxygen aging at 125 °C, compared to 66.89% under thermal-oil conditions. Infrared spectroscopy analysis further indicates enhanced nitro groups and alterations in other functional groups during aging, confirming oxidative chain scission and crosslinking reactions. This study provides quantitative experimental evidence for predicting the service life and optimizing the performance of nitrile rubber under severe environmental conditions. Full article

Water pollution from phenols remains a critical concern due to their persistence, toxicity, and industrial prevalence. Graphene oxide (GOx), with its functional groups and large surface area, offers strong adsorption potential. Using density functional theory (DFT), reduced density gradient (RDG), and quantitative structure–activity relationship (QSAR), we examined how protonation and substituents influence phenol adsorption. Deprotonated phenolates bind more strongly to GO than neutral species via electrostatics and H-bonding. Substituents alter affinity: halogens enhance it, bulky alkyls hinder it, and nitro groups show electron-withdrawing effects. Bisphenolate A displayed multidentate binding. QSAR models reproduced DFT energies with R² > 0.99, enabling fast prediction. These results highlight how pH speciation and substituents govern adsorption on GO, guiding the design of efficient water treatment materials. Full article

New aminonitrocyclitols were directly synthesized through stereoselective, one-pot, multistep cascade reactions. The aminonitrocyclitol moiety was constructed by the sequential action of two enzymes followed by a spontaneous intramolecular Henry reaction. To construct the carbocycle, two C–C bonds were stereoselectively cleaved, one by aldolase and the other by the intramolecular nitroaldol reaction. The aldolase acceptor substrates were generated by adding an amino group to 4-nitrobutanal. As expected, only the (R,R)- or d-erythroaldol configuration was obtained with l-fuculose-1-phosphate aldolase (F1PA). In the case of l-rhamnulose-1-phosphate aldolase (R1PA), both the aldol (R,S)- or l-threo and erythroaldol (R,R)- or d-erythroaldol configurations were obtained in very close ratios. The presence of a ketone and a terminal nitro group in the aldol formed led to a stereoselective intramolecular Henry reaction. The various aminonitrocyclitols were obtained in amide form with an average overall yield of 60%. Deprotection of the amine function was achieved by hydrolysis of the amide group by the action of papain without epimerization at the ring carbon stereochemistries defined in the previous steps. All these reactions led to the preparation of new aminonitrocyclitols with high stereoselectivity. Full article

In this paper we provide the Group Contribution parameters for acetylenes and aromatic nitro compounds fitting with a recently developed Group Contribution method with chemical accuracy (1 kcal/mol) for the heat of formation of organics. These additional parameters widen the applicability of the Group Contribution method. We also provide further G4 quantum calculated values as reference when no experimental data are available and compare to previously reported G4 data. Full article

A total of 250 known and novel compounds—ketamine and serotonergic psychedelics or their analogues—designed to target depression, addictions and/or other mental or neurological disorders and developed as “recreational” (illegal) drugs from three chemical families, ergolines, tryptamines and phenylethylamines, were investigated in the context of their ability to cross the human placenta. Using a novel multivariate model involving compounds’ drug-likeness (according to Lipinski’s Ro5), caco-2 membrane permeability, fraction unbound to plasma proteins, steady-state volume of distribution and the total count of heteroatoms (non-carbon atoms with hydrogens included), it was established that the majority of studied compounds are likely to cross the placenta easily, most probably by the passive diffusion mechanism. Atomic contributions of structural elements of studied compounds were investigated using the Morgan fingerprinting algorithm and it was postulated that the fragments promoting transport of compounds across the placenta are carbonyl, hydroxyl, nitro- and phosphoryloxy groups—rigid polycyclic structures, bulky alkyl/aryl groups and halogen atoms restrict the trans-placental passage. All studied compounds are expected to be relatively easily obtained by synthetic routes, which makes them an interesting target for manufacturers of illegal drugs and warrants the need to pursue pharmacological studies of these compounds in silico. Full article

Excessive oxidative stress within the renal medulla is implicated in the development of hypertension, potentially modulated by renal nerve stimulation (RNS). This study examined the effects of RNS on cortical and medullary blood perfusion in Stroke-Prone Spontaneously Hypertensive Rats (SHRSP) under both normal conditions and at varying levels of oxidative stress. Male SHRSP rats were assigned to five experimental groups and subjected to RNS at different frequencies, with infusions of vehicle, tempol, tempol plus catalase (tem + cat), diethyldithiocarbamic acid (DETC), or L-nitro-arginine methyl ester (L-NAME) at the renal cortico-medullary border (CMB). Regional blood perfusion of the renal cortex and medulla (CBP and MBP, respectively) was assessed using Laser-Doppler flowmetry. RNS significantly reduced CBP and MBP by 43 ± 8% and 23 ± 4%, respectively, at 8 Hz. Co-infusion of tempol plus catalase significantly attenuated the RNS-induced reductions in both CBP and MBP. Similarly, DETC infusion mitigated RNS-induced decreases in CBP and MBP. In contrast, tempol alone and L-NAME did not protect against the RNS-induced under-perfusion of the renal cortex and medulla. The results suggest that simultaneous removal of superoxide anion and hydrogen peroxide (H₂O₂) can alleviate the reduction in renal blood perfusion caused by RNS, emphasizing a crucial role for H₂O₂ in renal hemodynamic regulation. Interestingly, DETC, which is expected to elevate superoxide anion levels, also mitigated RNS-induced under-perfusion, suggesting the presence of a potentially novel indirect protective mechanism that warrants further investigation. Full article

Background/Objectives: Chagas disease remains a major unmet medical need due to the limited efficacy and safety of current therapies. Here, we investigated sixteen thiosemicarbazone (TSC) derivatives as cruzain inhibitors using an integrated in silico/in vitro workflow. Methods: Docking against cruzain (PDB 3KKU) guided hit prioritization and correlated with enzyme inhibition; validation by redocking supported the protocol’s reliability. Results: The top compounds—H7, H10 and H11—showed potent cruzain inhibition (IC₅₀ = 0.306, 0.512 and 0.412 µM, respectively) and low-micromolar trypanocidal activity, with negligible cytotoxicity in human fibroblasts (CC₅₀ > 64 µM) and favorable selectivity. Structure–activity insights highlighted the role of expanded aromatic systems and electron-donating groups in enhancing binding within S2/S1′ subsites, while nitro substituents were associated with higher cytotoxicity. In silico ADMET parameters supported oral drug-likeness and acceptable metabolic liabilities. Conclusions: Overall, these data position TSCs as promising anti-T. cruzi leads and underscore the value of rational design against cruzain. Full article

Hydroxyl-terminated polybutadiene (HTPB) is widely studied and the most used prepolymer for the binder system of composite solid propellants. A suitable functionalization of HTPB with energetic groups greatly improves the performance of the propellant. Therefore, the nitration of HTPB plays an essential role in the obtaining of high-energy binders. Among the reported methods, the nitration of HTPB using nitryl iodide (NO₂I) was distinguished as the most preferable due to the facilitated synthesis and product purity. However, the thus established synthesis is long and laborious; therefore, in the present work we focus our attention on the improved procedure using ultrasonic conditions. The resulted nitro-HTPB was characterized using FTIR, ¹H NMR, GPC, and DSC analyses. Also, based on the recorded IR-spectra a ratiometric analysis for determining the nitration rate was established, which could replace the expensive and time-consuming NMR analysis that was used. Full article

Background: In this study, we report a novel series of proline- and pipecolic acid-based small molecules designed as allosteric inhibitors of the NS2B/NS3 serine proteases from dengue and Zika viruses, key targets in antiviral drug discovery. Results: Enzymatic studies revealed that S-proline derivatives bearing electron-withdrawing substituents on the aromatic ring, particularly that with a trifluoromethyl group in meta position (i.e., compound 3, IC₅₀ = 5.0 µM), were the most potent against DENV NS2B/NS3, while nitro-substituted inhibitors were mostly effective only against the ZIKV protease. R-configured pipecolic acid-based derivatives were the only ones active against DENV NS2B/NS3, even if the mid-micromolar range; however, they demonstrated improved cellular efficacy since inhibitors 24 and 27 exhibiting strong activity in a DENV2 protease reporter gene assay (EC₅₀ = 5.2 and 5.1 µM, respectively). All compounds showed no cytotoxicity (CC₅₀ > 100 µM) and were selective for the viral protease over off-target serine proteases. Structure-based approaches were exploited to map the druggable allosteric site close to Asn152. Conclusions: Our findings led us to identify proline and pipecolic acid-based inhibitors as promising leads for the development of selective flaviviral NS2B/NS3 allosteric inhibitors. Full article

Failure of the endodontic treatment is often associated with persistent polymicrobial biofilms, particularly those involving Enterococcus faecalis (E. faecalis) and Candida albicans (C. albicans), which display synergistic pathogenicity and resistance to standard disinfection methods. This in vitro study compared the antimicrobial activity and oxidative damage induced by indocyanine green (ICG)–mediated laser ablation (LA) with that produced by antimicrobial photodynamic therapy (aPDT) using methylene blue (MB) or curcumin (CUR) in root canals infected with dual-species biofilms. The samples were divided into five experimental groups (n = 20): Group A—Methylene Blue + Red Laser (RL), Group B—Curcumin + Blue LED (BL), Group C—Indocyanine Green + Infrared Diode Laser (DL), Group D—saline solution (Negative Control—NC), Group E—2.5% sodium hypochlorite (Positive Control—PC). One hundred treated bovine incisors (20 per group) were analyzed for microbial viability (colony-forming unit (CFU/mL)), the metabolic functionality of biofilms was assessed through the 2,3-bis(2-methoxy-4-nitro-5-sulfophenyl)-5-[(phenylamino)carbonyl]-2H-tetrazolium hydroxide (XTT) based reduction method, and oxidative stress markers, including Thiobarbituric Acid Reactive Substances (TBARS), protein carbonyl content, total oxidant capacity (TOC), and total protein levels. All experimental treatments significantly reduced microbial load compared to the negative control (p < 0.05), with ICG achieving the greatest reduction. ICG also induced the highest levels of oxidative stress across all parameters (p < 0.05). These findings suggest that LA with ICG is more effective than aPDT with MB or CUR, achieving disinfection outcomes comparable to those of 2.5% sodium hypochlorite, and warrant further investigation in complex clinical models. Full article

Cassytha filiformis is a folkloric herbal medicine used to treat type 2 diabetes mellitus (T2DM). In this study, an oxidized aporphine alkaloid, designated as Filiforidine (3,10,11-trimethoxy-1,2-methylenedioxy-7-oxoaporphine), was isolated from C. filiformis, and its structure was elucidated through comprehensive spectroscopic analysis. Owing to its novel structure and significant glucose consumption activity, the total synthesis of Filiforidine was achieved for the first time. The key steps featured an electrophilic addition reaction, involving the reduction of a nitro group to an amino group with lithium tetrahydroaluminum, and a copper bromide-catalyzed oxidative aromatization reaction as well as a photocyclization reaction. Several experimental steps were optimized. Furthermore, a complex post-treatment method was developed, which reduced the column chromatography separation steps. Specifically, 2-(4-methoxybenzo[d][1,3]dioxol -5-yl) ethan-1-amine is salted with dilute hydrochloric acid. Cytotoxicity assay and glucose oxidase assay showed that Filiforidine had significant glucose consumption-promoting effects on HL-7702 cells at 0.625 μM, 1.25 μM, and 2.5 μM but without cytotoxicity. Therefore, Filiforidine might be a promising drug candidate for the treatment of diabetes. Full article