Explore the vast range of titles available.

Due to urbanization and industrialization, there has been an increase in solid waste generation and has become a global concern and leakage of leachate from landfills contaminate the soil and groundwater and hence can have a severe impact on human health. The present study aimed to determine the composition of toxic metals (Cr, Mn, Cu, As) and heavy metals (Cd, Ba, Hg, Pb) in soil and water by an inductively coupled plasma optical emission spectrometer (ICP-OES). To ensure accuracy during the analysis of Cr, Mn, Cu, As, Cd, Ba, Hg, and Pb in real samples, certified reference material (CRM, SRM 2709a) of San Joaquin soil and water (SRM 1640a) were analyzed and results were presented in terms of % recovery studies. The mean concentration of all the metals in soil and water did not exceed the limit set by the European Community (EU), WHO, and US EPA except Cu where the permissible limit defined by the EU is 50–140 mg/kg in soil. The soil is uncontaminated to moderately contaminated with respect to all metals except the Cu and Pb. Among the average daily dose (ADD) of soil, ADD ing and ADD inh for children had the maximum dose for all metals than adults while ADD derm was higher in adults. Hazard quotient (HQ) trend in both adults and children was found in order HQ ing  > HQ derm  > HQ inh of soil for all metals except Ba which followed HQ ing  > HQ inh  > HQ derm . Hazard index (HI) values of soil for Cr and Pb in children were 7 and 7.5 times higher than adults respectively. Lifetime cancer risk (LCR) value for Cr by different exposure pathways of soil was 5.361 × 10 −4 for children which are at the lower borderline of risk for cancer.

In this study, we developed a new chemi-resistive, flexible and selective ammonia (NH3) gas sensor. The sensor was prepared by depositing thin film of polyaniline-cobalt ferrite (PAni-CoFe2O4) nanocomposite on flexible polyethylene terephthalate (PET) through an in situ chemical oxidative polymerization method. The prepared PAni-CoFe2O4 nanocomposite and flexible PET-PAni-CoFe2O4 sensor were evaluated for their thermal stability, surface morphology and materials composition. The response to NH3 gas of the developed sensor was examined thoroughly in the range of 1–50 ppm at room temperature. The sensor with 50 wt% CoFe2O4 NPs content showed an optimum selectivity to NH3 molecules, with a 118.3% response towards 50 ppm in 24.3 s response time. Furthermore, the sensor showed good reproducibility, ultra-low detection limit (25 ppb) and excellent flexibility. In addition, the relative humidity effect on the sensor performance was investigated. Consequently, the flexible PET-PAni-CoFe2O4 sensor is a promising candidate for trace-level on-site sensing of NH3 in wearable electronic or portable devices.

Heavy and extra heavy oil exploitation has attracted attention in the last few years because of the decline in the production of conventional crude oil. The high viscosity of heavy crude oil is the main challenge that obstructs its extraction. Consequently, catalytic aquathermolysis may be an effective solution to upgrade heavy crude oil to decrease its viscosity in reservoir conditions. In this regard, a series of acidic ionic liquids, 1-butyl-1H-imidazol-3-ium 4-dodecylbenzenesulfonate (IL-4), 1-decyl-1H-imidazol-3-ium 4-dodecylbenzenesulfonate (IL-10), and 1-hexadecyl-1H-imidazol-3-ium 4-dodecylbenzenesulfonate (IL-16), were utilized in the aquathermolysis of heavy crude oil. Of each IL, 0.09 wt % reduced the viscosity of the crude oil by 89%, 93.7%, and 94.3%, respectively, after the addition of 30% water at 175 °C. ILs with alkyl chains equal to 10 carbon atoms or more displayed greater activity in viscosity reduction than that of ILs with alkyl chains lower than 10 carbon atoms. The molecular weight and asphaltene content of the crude oil were decreased after catalytic aquathermolysis. The compositional analysis of the crude oil before and after catalytic aquathermolysis showed that the molar percentage of lighter molecules from tridecanes to isosanes was increased by 26–45%, while heavier molecules such as heptatriacontanes, octatriacontanes, nonatriacontanes, and tetracontanes disappeared. The rheological behavior of the crude oil before and after the catalytic aquathermolytic process was studied, and the viscosity of the crude oil sample was reduced strongly from 678, 29.7, and 23.4 cp to 71.8, 16.9, and 2.7 cp at 25, 50, and 75 °C, respectively. The used ILs upgraded the heavy crude oil at a relatively low temperature.

A series of hydrazine-1-carbothioamides derivatives (3a–3j) were synthesized and analyzed for inhibitory potential towards bovine carbonic anhydrase II (b-CA II) and 15-lipoxygenase (15-LOX). Interestingly, four derivatives, 3b, 3d, 3g, and 3j, were found to be selective inhibitors of CA II, while other derivatives exhibited CA II and 15-LOX inhibition. In silico studies of the most potent inhibitors of both b-CA II and 15-LOX were carried out to find the possible binding mode of compounds in their active site. Furthermore, MD simulation results confirmed that these ligands are stably bound to the two targets, while the binding energy further confirmed the inhibitory effects of the 3h compound. As these compounds may have a role in particular diseases, the reported compounds are of great relevance for future applications in the field of medicinal chemistry.

Cancer is one of the leading causes of death worldwide. The increasing prevalence and resistance to chemotherapy is responsible for driving the search of novel molecules to combat this disease. In search of novel compounds with pro-apoptotic potential, pyrazolo-pyridine and pyrazolo-naphthyridine derivatives were investigated against cervical cancer (HeLa) and breast cancer (MCF-7) cells. The anti-proliferative activity was determined through the MTT assay. Potent compounds were then analyzed for their cytotoxic and apoptotic activity through a lactate dehydrogenase assay and fluorescence microscopy after propidium iodide and DAPI staining. Flow cytometry was used to determine cell cycle arrest in treated cells and pro-apoptotic effect was verified through measurement of mitochondrial membrane potential and activation of caspases. Compounds 5j and 5k were found to be most active against HeLa and MCF-7 cells, respectively. G0/G1 cell cycle arrest was observed in treated cancer cells. Morphological features of apoptosis were also confirmed, and an increased oxidative stress indicated the involvement of reactive oxygen species in apoptosis. The compound-DNA interaction studies demonstrated an intercalative mode of binding and the comet assay confirmed the DNA damaging effects. Finally, potent compounds demonstrated a decrease in mitochondrial membrane potential and increased levels of activated caspase-9 and -3/7 confirmed the induction of apoptosis in treated HeLa and MCF-7 cells. The present work concludes that the active compounds 5j and 5k may be used as lead candidates for the development of lead drug molecules against cervical and breast cancer.

Aurora kinases (AURKs) have been identified as promising biological targets for the treatment of cancer. In this study, molecular dynamics simulations were employed to investigate the binding selectivity of three inhibitors (HPM, MPY, and VX6) towards AURKA and AURKB by predicting their binding free energies. The results show that the inhibitors HPM, MPY, and VX6 have more favorable interactions with AURKB as compared to AURKA. The binding energy decomposition analysis revealed that four common residue pairs (L139, L83), (V147, V91), (L210, L154), and (L263, L207) showed significant binding energies with HPM, MPY, and VX6, hence responsible for the binding selectivity of AURKA and AURKB to the inhibitors. The MD trajectory analysis also revealed that the inhibitors affect the dynamic flexibility of protein structure, which is also responsible for the partial selectivity of HPM, MPY, and VX6 towards AURKA and AURKB. As expected, this study provides useful insights for the design of potential inhibitors with high selectivity for AURKA and AURKB.

Neurodegenerative disorders and neuroblastoma represent major therapeutic challenges, and multitarget approaches have gained increasing attention. In this study, a series of thiosemicarbazone derivatives (5a–t) was evaluated for their inhibitory activity against acetylcholinesterase (AChE), butyrylcholinesterase (BChE), and monoamine oxidase A (MAO-A), together with their cytotoxic effects and molecular interaction profiles. In vitro enzyme assays revealed nanomolar inhibition for several compounds. Notably, compound 5n exhibited potent and balanced multitarget activity with IC 50 values of 104.28 nM (AChE), 23.04 nM (BChE), and 215.50 nM (MAO-A), surpassing galantamine (IC 50  = 296.32 and 105.20 nM for AChE and BChE, respectively) and approaching the activity of clorgyline (IC 50  = 401.68 nM). Kinetic studies confirmed strong enzyme binding, with K i values of 92.42 nM (AChE) and 25.35 nM (BChE). Cytotoxicity assays against SH-SY5Y neuroblastoma cells showed selective antiproliferative effects, with compound 5n displaying an IC 50 of 5.23 µM and a selectivity index of 8.6 relative to HUVEC cells. Molecular docking and MM-GBSA analyses revealed strong binding affinities (docking scores − 10.4 to − 15.4 kcal/mol; ΔG_bind − 55.9 to − 88.4 kcal/mol), which were further supported by molecular dynamics simulations. DFT calculations indicated favorable electronic properties (HOMO–LUMO gap: 0.098–0.116 eV), while ADME predictions suggested acceptable drug-like behavior and good oral absorption. These results identify thiosemicarbazone derivative 5n as a promising multitarget lead for the development of agents targeting cholinergic dysfunction, MAO-A inhibition, and neuroblastoma proliferation.

A new series of 6-hydroxychromone-based thiosemicarbazones 4(a-p) was synthesized and assessed for their antidiabetic (α-Glucosidase and α-Amylase inhibition) as well as antioxidant (2,2-diphenyl-1-picrylhydrazyl (DPPH) and 2,2´-azinobis (3-ethylbenzothiazoline-6-sulfonic acid) (ABTS)) activities. Among the synthesized compounds, compound 4k (IC 50  = 1.18 ± 0.19 µg/mL) emerged as the promising α-Glucosidase inhibitor, significantly outperforming the reference drug Acarbose (IC 50  = 7.33 ± 0.13 µg/mL). For α-Amylase inhibition, compound 4 g (IC 50  = 13.61 ± 2.04 µg/mL) demonstrated excellent activity, compared to Acarbose (IC 50  = 43.15 ± 5.22 µg/mL). In antioxidant assays, compound 4o (IC 50  = 15.30 ± 1.70 µg/mL) exhibited the strongest DPPH radical scavenging effect, and compound 4 g (IC 50  = 6.06 ± 0.15 µg/mL) showed the highest ABTS scavenging activity, surpassing the standard antioxidant Trolox (IC 50  = 30.20 ± 5.14 & 18.19 ± 2.47 µg/mL, respectively). Remarkably, these derivatives showed greater efficacy compared to standard inhibitors, underscoring their promise as novel candidates for antidiabetic and antioxidant drug development. Molecular docking analysis demonstrated strong binding and critical interactions within the enzyme active sites. MD simulations confirmed the stability of 4k-α-Glucosidase and 4 g-α-Amylase, with RMSD values below 3.6 Å, low RMSF (< 2.8 Å) at the binding site, and sustained key interactions with Phe 158 and Tyr 151 , respectively. The network pharmacology further supported the findings of molecular docking and simulation analysis.

Ectonucleotidases, including NTPDases and ecto-5′-nucleotidase (e-5′NT/CD73), regulate extracellular purinergic signaling by converting ATP to adenosine, a pathway critically involved in immune response, inflammation, and cancer progression. In this study, a novel library of 22 N-propylsulfonyl-substituted indole-based hydrazinecarbothioamides (5a–5v) was synthesized and structurally characterized. Biological evaluation against human e-5′NT and NTPDase1, -2, -3, and − 8 revealed that several compounds exhibited low micromolar inhibitory activity, with 5n (IC 50  = 1.7 µM), 5o (IC 50  = 1.7 µM), 5f (IC 50  = 1.0 µM), and 5i (IC 50  = 1.6 µM) emerging as the most promising derivatives, showing strong potency and isoform selectivity. Structure–activity relationship analysis indicated that both electronic and steric features of substituents significantly influence activity and enzyme preference. Molecular docking studies performed on e-5′NT demonstrated that active compounds adopt consistent binding modes within the catalytic pocket, stabilized by key residues such as Asp-506, Phe-500, Phe-417 and Arg-395. Binding free energy calculations (MM-GBSA) supported strong ligand–protein interactions ( ~ − 70 kcal/mol). The docking protocol was validated by redocking, yielding an RMSD value well below the accepted threshold. Molecular dynamics simulations (500 ns) confirmed stable complex formation, with low RMSD values (~ 1–3 Å), limited residue fluctuations, and persistent interactions with catalytic residues. Surface and compactness parameters (rGyr, SASA) remained stable, indicating consistent ligand accommodation. In silico ADME analysis suggested favorable drug-like properties for most compounds, particularly for the lead candidates. Overall, these findings identify 5n and 5o as the most promising lead compounds, supported by both experimental and computational results, and highlight this scaffold as a valuable platform for the development of selective ectonucleotidase inhibitors.

A targeted delivery system is primarily intended to carry a potent anticancer drug to specific tumor sites within the bodily tissues. In the present study, a carrier system has been designed using folic acid (FA), bis-amine polyethylene glycol (PEG), and an anticancer drug, 5-fluorouracil (5-FU). FA and PEG were joined via an amide bond, and the resulting FA-PEG-NH2 was coupled to 5-FU producing folate-polyethylene glycol conjugated 5-fluorouracil (FA-PEG-5-FU). Spectroscopic techniques (UV-Vis, 1HNMR, FTIR, and HPLC) were used for the characterization of products. Prodrug (FA-PEG-5-FU) was analyzed for drug release profile (in vitro) up to 10 days and compared to a standard anticancer drug (5-FU). Folate conjugate was also analyzed to study its folate receptors (FR) mediated transport and in vitro cytotoxicity assays using HeLa cancer cells/Vero cells, respectively, and antitumor activity in tumor-bearing mice models. Folate conjugate showed steady drug release patterns and improved uptake in the HeLa cancer cells than Vero cells. Folate conjugate treated mice group showed smaller tumor volumes; specifically after the 15th day post-treatment, tumor sizes were decreased significantly compared to the standard drug group (5-FU). Molecular docking findings demonstrated importance of Trp138, Trp140, and Lys136 in the stabilization of flexible loop flanking the active site. The folic acid conjugated probe has shown the potential of targeted drug delivery and sustained release of anticancer drug to tumor lesions with intact antitumor efficacy.