Chitosan-sulfonic acid-catalyzed green synthesis of naphthalene-based azines as potential anticancer agents.

Aim: This study focuses on advancing green chemistry in anticancer drug discovery, particularly through the synthesis of azine derivatives with a naphthalene core using CS-SO3H as a catalyst. Methods: Novel benzaldazine and ketazine derivatives were synthesized using (E)-(naphthalen-1-ylmethylene)hydrazine and various carbonyl compounds. The methods employed included thermal and grinding techniques, utilizing CS-SO3H as an eco-friendly and cost-effective catalyst. Results: The approach resulted in high yields, short reaction times and demonstrated catalyst reusability. Cytotoxicity tests highlighted compounds 3b, 11 and 13 as potent against the HEPG2-1. Conclusion: This study successfully aligns with the objectives of eco-conscious drug development in organic chemistry. Molecular docking and in silico studies further indicate the potential of these ligands as antitumor medicines, with favorable oral bioavailability properties.

Facile synthesis and eco-friendly analytical methods for concurrent estimation of selected pharmaceutical drugs in their solutions: application to quality by design, lean six sigma, and stability studies.

Economical, highly robust, selective, precise, and eco-friendly RP-UPLC and spectrophotometric methods were developed and validated for the concurrent estimation of selected pharmaceutical drugs represented in ceftazidime (CFZ) and pyridine (PYD) in their solutions using Agilent Zorbax SB-C18 RRHD (50 × 2.1 mm, 1.8 µm) column at flow rate 0.3 mL/min with wavelength 254 nm. Box-Behnken design (BBD) established Response surface methodology (RSM) to achieve the optimum chromatographic condition with minimal trials conducted. Three independent variables specifically acetonitrile ratio 60-70%, pH 3-7, and temperature 25-35 °C were implemented to evaluate the influences of these variables on the responses as resolution and retention time. Desirability and overlay plots were carried out to adjust the optimal condition that achieved the shortest retention time of less than 2 min and desired resolution of more than 1.5 using a mobile phase consisting of acetonitrile: purified water (70:30, v/v) at pH 5.0 adjusted by 0.1% orthophosphoric acid with the column oven temperature 30 °C and column void volume 0.46 mL. Mean centering of ratio spectra (MCR) and ratio subtraction (RS) methods were effectively applied to resolve drugs' spectral superposition at 220 nm, 255.4 nm, 260.3 nm, and 254.6 nm for CFZ and PYD, respectively. Linearity range was accomplished for UPLC, MCR, and RS methods over the concentration range of 2-100, 1-50,3-30 and 5-30 µg/mL for CFZ and PYD, respectively with correlation coefficient > 0.999 and good recovery results within 98-102%. Six Sigma methodology was achieved using the process capability index (Cpk) to compare the suggested and USP methods showing that both are highly capable with Cpk > 1.33. The proposed method was successfully validated depending on ICH guidelines and ANOVA results and applied for the accelerated stability study.

An Effective Chromatographic Method for Simultaneous Quantification of Antidiabetic Drugs Alogliptin Benzoate and Pioglitazone HCl in Their Tablet Dosage Form: Implementation to In vitro Dissolution Studies and Uniformity of Dosage Unit.

In patients with Type 2 diabetes, a combination of Alogliptin and Pioglitazone medications, together with diet and physical activity, are used to improve glycemic control. Eco-friendly, cost-effective, and precise stability-indicating RP-HPLC method was developed and validated for the identification and quantification of Alogliptin and Pioglitazone in their tablet dosage form, as well as implementation to in vitro dissolution studies and uniformity of dosage unit. Isocratic separation is conducted at ambient temperature on the InertSustain C18 Analytical Column (150 × 4.6 mm, 5 µm) using mobile phase comprising 50 mM of ammonium dihydrogen phosphate and 5.0 mM of heptane sulfonic acid:acetonitrile (45:55, v/v) at a flow rate of 1.3 mL/minute. Calibration curves are conducted in the linearity range of 1-40 µg/mL of Alogliptin and 2.5-75 µg/mL of Pioglitazone with a correlation value >0.9995 and satisfactory recovery findings between 99 and 100%. The degraded samples are analyzed under relevant stress conditions as acidity, alkalinity, thermal and oxidation. The active components in finished products were subjected to a content uniformity test, which showed that they achieved the declared claim's acceptance standards (85-115%). Comparative in vitro dissolution studies are performed for generic products Inhibazone 12.5/30 mg FCT and Inhibazone 25/15 mg FCT against innovator products Oseni 12.5/30 mg FCT and Oseni 25/15 mg FCT at suitable FDA dissolution medium and different USP dissolution media and the results are similar. The metrics of the designed method were assessed according to ICH requirements, and all metrics, such as system suitability, linearity, recovery, robustness, LOD, LOQ, specificity and precision, were found to be within required tolerances and no overlapping was found for degradation peaks. Thence, the method can be used in quality control for the analysis of raw material, bulk, finish and stability.

Cross-Linked Chitosan/Gelatin Beads Loaded with Chlorella vulgaris Microalgae/Zinc Oxide Nanoparticles for Adsorbing Carcinogenic Bisphenol-A Pollutant from Water.

Water polluted by phenolic compounds is a global threat to health and the environment; accordingly, we prepared a green novel sorbent biological system from a chitosan (CS), gelatin (GT), and Chlorella vulgaris freshwater microalgae (m-Alg) composite impregnated with zinc oxide nanoparticles (ZnO-NPs) for the remediation of bisphenol-A (BPA) from water. C. vulgaris was selected to be one of the constituents of the prepared composite because of its high capability in phytoremediation. The morphology and the structure of CS/GT*m-Alg/ZnO beads were characterized by SEM, FTIR, XRD, and TGA. Different monitoring experimental conditions, such as contact time, pH, BPA concentration, and sorbent dosage, were optimized. The optimum conditions for the adsorption process showed outstanding removal efficiency toward BPA at pH 4.0, contact time 40.0 min, and 40.0 mg L-1 BPA initial concentration. Langmuir, Freundlich, and Temkin isotherm models have been studied for adsorption equilibrium, and the best fit is described by the Langmuir adsorption isotherm. The adsorption kinetics has been studied using pseudo-first-order (PFO), pseudo-second-order (PSO), Elovich, and intraparticle diffusion (IPD) models. The pseudo-second-order kinetic model shows the optimum experimental fit. The monolayer adsorption capacity of the prepared CS/GT*m-Alg/ZnO for BPA was determined to be 38.24 mg g-1. The prepared CS/GT*m-Alg/ZnO beads show advantageous properties, such as their high surface area, high adsorption capacity, reusability, and cost-effectiveness.

Alginate/κ-carrageenan oral microcapsules loaded with Agaricus bisporus polysaccharides MH751906 for natural killer cells mediated colon cancer immunotherapy.

The current study explores the effect of the extracted novel Mushroom polysaccharides and its formulation onto Alginate (Alg.)/kappa carrageenan microcapsules to exert immunotherapeutic effect upon activating gut resident natural killer cells (NK) against colon cancer. The extracted polysaccharides of Agaricus bisporus MH751906 was microcapsulated in Alg/κ-carrageenan microcapsules as an oral delivery system for colon cancer. The microcapsule is characterized by SEM, FTIR, Raman and TGA; and showed a superior acidic stability, controlled release, and thermal stability at high temperature with higher hydrogel swelling rate in colon-mimicking pH. Upon activation of human NK cells with microcapsules (ANK cells), a significant increase in CD16+CD56+ NK cell populations were recorded. These activated NK cells showed 74.09% cytotoxic effects against human colon cancer Caco-2 cells where majority of cancer cell populations arrested at G0/G1 phase leading to apoptosis. The apoptotic molecular mechanism induced by ANK cells on Caco-2 treated cells is through down regulations of both BCL2 and TGF surviving genes and up regulation in IkappaB-α gene expression. Therefore, this novel polysaccharides-alginate/κ-carrageenan microcapsules can be used as an oral targeted delivery system for colon cancer immunotherapy.

Synthesis, Antibacterial, and Anti HepG2 Cell Line Human Hepatocyte Carcinoma Activity of Some New Potentially Benzimidazole-5-(Aryldiazenyl)Thiazole Derivatives.

The paper describes the synthesis and biological evaluation of some new benzimidazole derivatives as potent clinical drugs that are useful in the treatment of some microbial infections and tumor inhibition. The starting compound 2-(bromomethyl)-1H-benzimidazole (1) was prepared, and hence underwent interesting functionalization reactions to afford several series of benzimidazole-5-(aryldiazenyl)thiazole derivatives: 3a⁻c, 7a⁻c, and 8a⁻c. The antibacterial activities of the synthesized compounds were evaluated by calculation of the inhibition zone diameter (mm) and the determination of minimum inhibitory concentration (µg/mL) against selected pathogenic bacteria Staphylococcus aureus (Gram-positive bacteria) and Escherichia coli (Gram-negative bacteria).Noticeable efficiency was found based on in vitro screening for their antioxidant activity and cytotoxicity effect against the human liver cancer cell line (HepG2) and human hepatocyte carcinoma cells at relatively high concentrations.

Spectroscopic, thermodynamic, kinetic studies and oxidase/antioxidant biomimetic catalytic activities of tris(3,5-dimethylpyrazolyl)borate Cu(II) complexes.

A series of copper(ii) complexes, viz. [Tp(MeMe)Cu(Cl)(H2O)] (), [Tp(MeMe)Cu(OAc)(H2O)] (), [Tp(MeMe)Cu(NO3)] () and [Tp(MeMe)Cu(ClO4)] () containing tris(3,5-dimethylpyrazolyl)borate (KTp(MeMe)), have been synthesized and fully characterized. The substitution reaction of with thiourea was studied under pseudo-first-order conditions as a function of concentration, temperature and pressure in methanol and acetonitrile as solvents. Two reaction steps that both depended on the nucleophile concentration were observed for both solvents. Substitution of coordinated methanol is about 40 times faster than the substitution of chloride. In acetonitrile, the rate constant for the displacement of coordinated acetonitrile was more than 20 times faster than the substitution of chloride. The reported activation parameters indicate that both reaction steps follow a dissociative mechanism in both solvents. On going from methanol to acetonitrile, the rate constant for the displacement of the solvent becomes more than 200 times faster due to the more labile acetonitrile, but the substitution mechanism remained to have a dissociative character. The antioxidant activities of were evaluated for superoxide dismutase (SOD), glutathione-s-transferase (GST0 and glutathione reduced (GSH-Rd) activity. and were found to show (p < 0.05) the highest antioxidant activity in comparison to and , which can be ascribed to the geometric configuration as well as the nature of the co-ligand. showed catechol oxidase activity with turnover numbers of 20 min(-1) and a coordination affinity for 3,5-DTBC of K1, = 31 mM(-1). K1 is rather large and seems to be typical for faster biomimetic models, and also for the enzyme itself (25 mM(-1)). The reaction rate depended linearly on the complex concentration, indicating a first-order dependence on the catalyst concentration.

Synthesis and anti-tumor activities of some new pyridines and pyrazolo[1,5-a]pyrimidines.

Cyclocondensation of cyanoacetamide, cyanothioacetamide and 3-aminopyrazols with sodium salt of 3-hydroxy-1-(2-naphthyl)prop-2-en-1-one gives pyridin-2-one, pyridin-2(1H)-thione, and pyrazolo[1,5-a]pyrimidine derivatives. These derivatives showed potent anti-tumor cytotoxic activity in vitro using different human cancer cell lines.

Epigenetic events, remodelling enzymes and their relationship to chromatin organization in prostatic intraepithelial neoplasia and prostatic adenocarcinoma.

OBJECTIVE: To explore the nuclear chromatin phenotype, overall epigenetic mechanisms, chromatin remodelling enzymes and their role as diagnostic biomarkers in prostate lesions, using high-resolution computerized quantitative digital image analysis (DIA). MATERIALS AND METHODS: A tissue microarray (TMA) was constructed using paraffin wax-embedded prostatic tissues from 78 patients, containing 30 cores of benign prostatic hyperplasia (BPH), 10 of low-grade prostatic intraepithelial neoplasia (LGPIN), 38 of prostate adenocarcinoma, 20 of BPH tissue excised at 0.6-1 mm from LGPIN lesions, and 10 of BPH prostatic tissues obtained 0.6-1 mm from high-grade PIN (HGPIN) lesions. Chromatin phenotype was assessed on haematoxylin-stained sections using high-resolution texture analysis. For quantitative immunohistochemistry, antibodies raised against acetylated histone H3 lysine 9 (AcH3K9), 5'methylcytidine (5MeC) and the chromatin remodelling ATPase ISWI (SNF2H and SNF2L) were used. The immunodensity was measured using DIA to determine the epigenetic profile of the cases. At least 60 nuclei were measured from each case. RESULTS: There were many statistically significant differences in staining intensity and nuclear distribution patterns in chromatin phenotype and immunostaining (p

Solid-phase extraction combined with high-performance liquid chromatography-atmospheric pressure chemical ionization-mass spectrometry analysis of pesticides in water: method performance and application in a reconnaissance survey of residues in drinking water in Greater Cairo, Egypt.

Monitoring of water resources for pesticide residues is often needed to ensure that pesticide use does not adversely impact the quality of public water supplies or the environment. In many rural areas and throughout much of the developing world, monitoring is often constrained by lack of testing facilities; thus, collection of samples and shipment to centralized laboratories for analysis is required. The portability, ease of use, and potential to enhance analyte stability make solid-phase extraction (SPE) an attractive technique for handling water samples prior to their shipment. We describe performance of an SPE method targeting a structurally diverse mixture of 25 current-use pesticides and two common degradates in samples of raw and filtered drinking water collected in Greater Cairo, Egypt. SPE was completed in a field laboratory in Egypt, and cartridges were shipped to the United States for elution and high-performance liquid chromatography-atmospheric pressure chemical ionization-mass spectrometry analysis. Quantitative and reproducible recovery of 23 of 27 compounds (average = 96%; percent relative standard deviation = 21%) from matrix spikes (1 microg L-1 per component) prepared in the field and from deionized water fortified similarly in the analytical laboratory was obtained. Concurrent analysis of unspiked samples identified four parent compounds and one degradate in drinking water samples. No significant differences were observed between raw and filtered samples. Residue levels in all cases were below drinking water and "harm to aquatic-life" thresholds, indicating that human and ecological risks of pesticide contamination were relatively small; however, the study was limited in scale and scope. Further monitoring is needed to define spatial and temporal variation in residue concentrations. The study has demonstrated the feasibility of performing studies of this type using SPE to extract and preserve samples in the field. The approach should be broadly applicable in many settings.