Lipophilic Character Research Articles

S-metolachlor in pre-emergence reduces the leaf cuticular wax and increases the efficiency of glyphosate.

The low glyphosate uptake capacity, possibly due to the lipophilic character of epicuticular wax on leaves, may contribute to the natural tolerance of some weed species. The use of pre-emergence herbicides like S-metolachlor, which inhibits very-long-chain fatty acid synthesis, might enhance glyphosate's post-emergent efficacy against hard-to-control weeds, such as Euphorbia heterophylla L. (milkweed) and Ipomoea triloba L. (littlebell). This study aimed to determine whether S-metolachlor affects glyphosate's efficacy and its impact on epicuticular wax production in these species. In Experiment 1, milkweed was 2.27 times more tolerant to S-metolachlor than littlebell, with GR50 values of 1024.6 g ai ha-1 and 451.2 g ai ha-1, respectively. In Experiment 2, S-metolachlor enhanced glyphosate efficacy in both species. For littlebell, S-metolachlor increased glyphosate efficacy by 28% at 21 days after treatment (DAT), while milkweed boosted control to 61%, compared to 45% in untreated plants. The herbicide accelerated glyphosate's action, particularly at lower doses. In Experiment 3, S-metolachlor reduced epicuticular wax by up to 47% in littlebell and 45% in milkweed during early growth. Wax levels remained lower in treated plants, contributing to improved glyphosate efficacy. S-metolachlor in pre-emergence reduces the amount of wax deposited in the leaf surface, increasing glyphosate efficiency in both species, especially at the beginning of the phenological stage. © 2024 Society of Chemical Industry.

Investigation of the anticancer potential of newly synthesized N4-substituted thiosemicarbazones: In silico and in vitro biological approaches

Four thiosemicarbazones by using tolualdehyde and cuminaldehyde having the formula, R2−(S)C−HN−N=HC−R2 [R1 = CH3 & R2 = C4H9N (TAP), R2 = C4H9NO & R1 = CH3 & (TAM), R2 = C4H9N & R1 = (CH3)2CH (CMP), R2 = C4H9NO & R1 = (CH3)2CH (CMM)] have been synthesized. The compound interactions were assessed using their UV−visible, infrared, NMR, and HRMS spectra. Single−crystal X−ray diffraction was employed to know the molecular structure of CMP and TAP. The compounds were assessed for their interactions with Calf−Thymus (CT)−DNA using spectroscopic titrations using both emission and absorption spectra. As per the research findings on DNA binding, the compounds interactively interacted with DNA, as indicated by the hypochromic and slight red shift. TAP exhibited a high binding constant (5.16 × 105), suggesting a stronger binding to CT−DNA compared to other compounds. The fluorescence titration spectra of BSA binding experiments exhibited a noteworthy hypochromic shift and red shift, displaying a strong interaction of chemicals with BSA. EGFR protein docking examination demonstrated the potential of compounds to treat the targets. TAP displayed the highest binding score (–6.4230 Kcal/mol) to EGFR with the four compounds. To compute density functional theory (DFT), B3LYP/6−311 G (d, p) level theories have been implemented. Generated compounds' computational analyses reveal the structural stability of compound TAP than the rest synthesized ligands. SwissADME investigations indicate that the LogP values for each compound are less than five indicating that they have the right lipophilicity characteristics. All newly synthesized compounds follow Lipinski's rule of drug lines. A good result for this characteristic is indicated by the low degree of synthetic accessibility, which falls between two and three. Each of the compounds (TAP−CMM) can develop into a viable oral medicine. Each compound (TAP−CMM) was tested for its anticancer potential using MCF−7, MCF−10A, A549, and human HepG−2 liver. TAP demonstrated favorable efficacy in HepG−2 liver cancer cells, exhibiting IC50 values of 23.1 μM.

In Vitro Evaluation of New 5-Nitroindazolin-3-one Derivatives as Promising Agents against Trypanosoma cruzi

Chagas disease is a prevalent health problem in Latin America which has received insufficient attention worldwide. Current treatments for this disease, benznidazole and nifurtimox, have limited efficacy and may cause side effects. A recent study proposed investigating a wide range of nitroindazole and indazolone derivatives as feasible treatments. Therefore, it is proposed that adding a nitro group at the 5-position of the indazole and indazolone structure could enhance trypanocidal activity by inducing oxidative stress through activation of the nitro group by NTRs (nitroreductases). The study results indicate that the nitro group advances free radical production, as confirmed by several analyses. Compound 5a (5-nitro-2-picolyl-indazolin-3-one) shows the most favorable trypanocidal activity (1.1 ± 0.3 µM in epimastigotes and 5.4 ± 1.0 µM in trypomastigotes), with a selectivity index superior to nifurtimox. Analysis of the mechanism of action indicated that the nitro group at the 5-position of the indazole ring induces the generation of reactive oxygen species (ROS), which causes apoptosis in the parasites. Computational docking studies reveal how the compounds interact with critical residues of the NTR and FMNH2 (flavin mononucleotide reduced) in the binding site, which is also present in active ligands. The lipophilicity of the studied series was shown to influence their activity, and the nitro group was found to play a crucial role in generating free radicals. Further investigations are needed of derivatives with comparable lipophilic characteristics and the location of the nitro group in different positions of the base structure.

Exploring the Microbial Inhibition Ability of Newly Synthesized Diorganotin(IV) Complexes of Hydrazone Ligands: Structural Elucidation, Crystal Structure, and DFT Studies

ABSTRACTIn our work, we have successfully synthesized twelve diorganotin(IV) complexes (4–15) from different hydrazone ligands and diorganotin(IV) dichlorides. The complexes have a general formula [R2SnL1–3], where R = Et, Me, Bu, and Ph groups. The hydrazone ligands (1–3) were synthesized through a condensation reaction involving 3‐ethoxysalicylaldehyde with different benzhydrazide derivatives. All the synthesized hydrazone ligands and their complexes underwent screening by employing numerous spectroscopic and physicochemical techniques, such as molar conductance measurements, mass spectrometry, (1H, 119Sn, and 13C) NMR, SEM‐EDAX, and FT‐IR. Spectroscopic analysis revealed that the hydrazone ligands were attached to tin atoms in a tridentate fashion via ONO donor atoms, suggesting a pentacoordinated geometry for the complexes. Furthermore, the X‐ray crystallography analysis for Complex 6 revealed the distorted square pyramidal geometry around the tin atom. Moreover, a DFT study was also carried out for Ligand 3 and its complexes (12–15) by employing B3LYP/LanL2DZ theory level (Gaussian 9 software package) to obtain the optimized geometry and global reactivity descriptors, structural behavior, and their efficacy against different microbes. To assess the biological efficacy of synthesized compounds, an in vitro antimicrobial assay was conducted against different fungal (Aspergillus niger and Candida albicans) and bacterial (Staphylococcus aureus, Bacillus subtilis, Escherichia coli, and Pseudomonas aeruginosa) strains. The results of the antimicrobial assay demonstrated that Complexes 7, 11, and 15 depicted better results against E. coli strain and C. albicans strain, implying that the higher lipophilic character of these complexes facilitates their easy passage through the cell membrane of microbes. Furthermore, an ADMET study was carried out to evaluate the toxicity score of synthesized compounds.

Aldose Reductase Evaluation against Diabetic Complications Using ADME and Molecular Docking Studies and DFT Calculations of Spiroindoline Derivative Molecule

In this study, the target molecule ethyl-2-(5-nitro-5'-(4-nitrophenyl)-2-oxo-3'H-spiro[indoline-3,2'-[1,3,4]oxadiazol]-1-yl)acetate, which is a spiroindoline derivative, were performed NBO analysis, molecular electrostatic potential surface (MEPS), nonlinear optics (NLO), HOMO-LUMO energy calculations, optimized molecular geometry, and mulliken atomic charges using B3LYP/B3PW91 basis set and 6-311G(d,p) approximations. Calculated results were reported. Density Functional Theory (DFT) computations were utilized to research the molecule theoretically. Moreover, molecular docking analysis of the tested compound, a spiroindoline derivative molecule targeting aldose reductase against diabetic complications, was performed using molecular docking to determine the structure-activity connection. The molecular docking study provided important information worth considering for further research. A notable outcome of bioisosteric and isosteric substitutions is the alteration in lipophilic character, an impressive characteristic in several aspects. Thus, utilizing SwissADME, lipophilic character assessments were performed for the concerned compounds.

Design, synthesis, and biological evaluation of novel halogenated chlorido[N,N′-bis(salicylidene)-1,2-bis(3-methoxyphenyl)ethylenediamine]iron(III) complexes as anticancer agents

Iron(III) complexes based on N,N´-bis(salicylidene)ethylenediamine (salene) scaffolds have demonstrated promising anticancer features like induction of ferroptosis, an iron dependent cell death. Since poor cellular uptake limits their therapeutical potential, this study aimed to enhance the lipophilic character of chlorido[N,N′-bis(salicylidene)-1,2-bis(3-methoxyphenyl)ethylenediamine]iron(III) complexes by introducing lipophilicity improving ligands such as fluorine (X1), chlorine (X2) and bromine (X3) in 5-position in the salicylidene moieties. After detailed characterization the binding to nucleophiles, logP values and cellular uptake were determined. The complexes were further evaluated regarding their biological activity on MDA-MB 231 mammary carcinoma, the non-tumorous SV-80 fibroblast, HS-5 stroma and MCF-10A mammary gland cell lines. Stability of the complexes in aqueous and biological environments was proven by the lack of interactions with amino acids and glutathione. Cellular uptake was positively correlated with the logP values, indicating that higher lipophilicity enhanced cellular uptake. The complexes induced strong antiproliferative and antimetabolic effects on MDA-MB 231 cells, but were inactive on all non-malignant cells tested. Generation of mitochondrial reactive oxygen species, increase of lipid peroxidation and induction of both ferroptosis and necroptosis were identified as mechanisms of action. In conclusion, halogenation of chlorido[N,N′-bis(salicylidene)-1,2-bis(3-methoxyphenyl)ethylenediamine]iron(III) complexes raises their lipophilic character resulting in improved cellular uptake.Graphical abstract

Parabens, bisphenols, and triclosan in coral polyps, algae, and sediments from sanya, China: Occurrence, profiles, and environmental implications

Parabens, bisphenols (BPs), and triclosan (TCS) are common environmental phenols widely applied in industrial products, pharmaceuticals, and personal care products. They are endocrine disruptors and pervade the natural environment, causing significant detrimental impacts on ecosystems, including marine habitats. Therefore, in this study, 40 samples comprising coral polyps, algae, and sediments were collected from Sanya, Hainan Province, China, in which the presence and compositional profiles of parabens, BPs, and TCS were examined to identify their fate in the oceans. The results unveiled the ubiquitous occurrence of at least one paraben or bisphenol in all samples, with TCS detected in over 80% of cases. Notably, coral samples contained the most contaminants (median concentration: 9.42 ng/g dry weight-dw), followed by sediment samples (5.95 ng/g dw) and algal samples (3.58 ng/g dw). Attributed to their broadest application, methylparaben (MeP) and propylparaben (PrP) emerged as the primary paraben constituents. MeP displayed the highest median concentration in coral samples (4.42 ng/g dw), probably related to its high-water solubility and the filtration mechanism employed by the coral polyps during seawater intake. Intriguingly, bisphenol P (BPP) superseded bisphenol A (BPA) as the dominant bisphenol, especially in the algal samples, probably owing to the lipophilic character of BPP and the enhanced biodegradability of BPA within aquatic environments. The highest concentration of TCS (3.44 ng/g dw) was found in the sediment samples, associated with its long half-life in the sediments. Furthermore, the correlation between multiple parabens and TCS implies their co-use to augment antimicrobial efficacy. Future research should prioritize the examination of these phenols in diverse marine environmental media. Corresponding toxicological experiments should be conducted to visualize their transport dynamics, degradation byproducts, and toxicity to marine biota to gain insights into the risks they pose to the marine ecosystem.

Capsaicin: Emerging Pharmacological and Therapeutic Insights.

Capsaicin, the most prominent pungent compound of chilli peppers, has been used in traditional medicine systems for centuries; it already has a number of established clinical and industrial applications. Capsaicin is known to act through the TRPV1 receptor, which exists in various tissues; capsaicin is hepatically metabolised, having a half-life correlated with the method of application. Research on various applications of capsaicin in different formulations is still ongoing. Thus, local capsaicin applications have a pronounced anti-inflammatory effect, while systemic applications have a multitude of different effects because their increased lipophilic character ensures their augmented bioavailability. Furthermore, various teams have documented capsaicin's anti-cancer effects, proven both in vivo and in vitro designs. A notable constraint in the therapeutic effects of capsaicin is its increased toxicity, especially in sensitive tissues. Regarding the traditional applications of capsaicin, apart from all the effects recorded as medicinal effects, the application of capsaicin in acupuncture points has been demonstrated to be effective and the combination of acupuncture and capsaicin warrants further research. Finally, capsaicin has demonstrated antimicrobial effects, which can supplement its anti-inflammatory and anti-carcinogenic actions.

Novel tributyl phosphate-based deep eutectic solvent: Application in microwave assisted extraction of carotenoids

A contribution to the use of deep eutectic solvents (DES) and microwave-assisted extraction (MAE) was made for bioactive compounds recovery, especially those with lipophilic character, from tomato and carrot samples rich in carotenoids. For the first time, a novel deep eutectic solvent was synthesized, comprising tributyl phosphate (TBP) as a hydrogen bond acceptor and acetic acid (AcOH) as a hydrogen bond donor. The total antioxidant capacity (TAC) of tomato and carrot extracts obtained by MAE, in which optimization of operational parameters and modeling were made with the use of Box-Behnken design of the response surface methodology (RSM), was evaluated using the Cupric Reducing Antioxidant Capacity (CUPRAC) method. For the highest TAC, operational parameters that best suit the MAE procedure were set at 80 °C, 35 min, and 25 mL/2.0 g. The TAC values of extracts obtained by MAE using TBP:AcOH, 1:2 (mol/mol) were examined against those of extracts acquired by classical solvent extraction using a mixture of hexane, ethanol and acetone (H:E:A, 2:1:1 (v/v/v)) mixture. TAC of extracts in DES varied between 5.10 and 0.71 lycopene equivalents (mmol LYC kg−1). The highest extraction yield comparable to conventional organic solvents was obtained with TBP:AcOH (1:2). It was observed that, in addition to lipophilic antioxidants, some hydrophilic antioxidant compounds were partially extracted with the proposed DES. Moreover, the extracted antioxidant compounds were identified and quantified by HPLC analysis. The proposed DES and MAE process will find potential application for hydrophobic antioxidant extraction from tomatoes and carrots on an industrial scale after further studies.

Boosting solvent resistance and structure stability of degradable polyester through extended-chain crystal structure: A preliminary case of oil/water separation membrane

Developing polymer-based oil/water separation membranes has emerged as a promising approach for wastewater, and fabrication of environmental-friendly separation membranes is becoming a vital issue for sustainable development. Currently, the application of degradable polyesters for oil/water separation is severely limited due to their inferior resistance to various solvents. Herein, we report a new kind of separation membrane of degradable aliphatic polyester based on extended-chain crystals. Though significant improvements in the crystalline structure, including crystallinity and thermodynamic stability, the polyester membranes gain outstanding solvent resistance, maintaining their structural integrity even after prolonged immersion in diverse solvents for up to 100 days. Meanwhile, the hydrophobic and lipophilic characteristic of aliphatic polyester is well inherited in the separation membrane, imparting exceptional wettability to various solvents. Consequently, the extended-chain crystal porous membranes exhibit excellent flux performance and good separation efficiency for solvent and water mixtures and emulsions. In addition, the extended-chain crystal structure gives the membrane outstanding mechanical properties. This work provides the first membrane application report of extended-chain crystal in degradable aliphatic polyester and reveals the potential of extended-chain crystal materials to deliver superior performance and extensive application.

Characterization and Animal Skin Irritations Investigation of Vemurafenib Microemulsion-Based Hydrogel Using Oily Ionic Liquid

Cutaneous melanoma accounts for a yearly mortality rate of 55,500 persons. The use of oral small-molecule kinase inhibitors, specifically targeting BRAFv600, has been licensed as the principal treatment strategy for managing both locally progressed and metastatic presentations of the condition. Approximately 30% of people on vemurafenib, a BRAFv600 inhibitor, have side effects when are taken orally. Objective: This research was attempted to develop a vemurafenib microemulsion by substituting conventional oil phases with ionic liquids (ILs). The microemulsions were created by dissolving vemurafenib in a combination of ionic liquid (1-Butyl-3-methylimidazolium hexafluorophosphate and 1-Octyl-3-methylimidazolium hexafluorophosphate) and surfactant (Triton x-100). Multiple tests were conducted to measure physical stability, pH determination, content homogeneity examination, and in vitro medicine release analysis. Four formulations of Vemurafenib microemulsions successfully met all criteria in the microemulsion characterisation and assessment tests. The droplet sizes in these microemulsions fell inside the range of microemulsions, which is less than 200 nm. They were then used to create microemulsion-based hydrogels, employing Carbamer 340 as a gelling agent by conducting a simple mixing method. Hydrogels formed from microemulsions containing 1-Octyl-3-methylimidazolium hexafluorophosphate demonstrated the ability to form clear hydrogels with desirable consistency. Regarding Ex-vivo permeability study and skin deposition the permeability profiles of GOT3 formula exhibits a permeability measurement of 33569± 344 mP.s at 6 rpm, whereas GOT4 demonstrates a permeability measurement of 54723± 380 mP.s at 6 rpm. During the skin irritation test, there was no apparent erythema and edema were observed when compared to the negative group. This may indicate that the designed microemulsion-based gel formulation demonstrates good biocompatibility with skin tissue. Topical delivery of vemurafenib is a promising route of drug administration to melanoma skin. Ionic liquids (ILs) have permeation-enhancing properties with either hydrophilic or lipophilic characteristics‎‎‎‎‎.

Impact of deodorisation time and temperature on the removal of different MOAH structures: a lab-scale study on spiked coconut oil

Vegetable fats and oils are prone to contamination by mineral oil hydrocarbons due to the lipophilic and ubiquitous character of the latter. As the aromatic fraction of these hydrocarbons, MOAH, is associated with carcinogenicity, mutagenicity, and detrimental effects on foetal development, finding strategies to limit or reduce their contamination is highly relevant. Deodorisation (i.e. a refining step) has shown the ability to remove MOAH < C25 in vegetable fats and oils, but there is little information about the structures removed. Therefore, the present study investigated the impact of deodorisation conditions on the removal of different structures of MOAH in spiked coconut oil. An inscribed central composite design was built with time and temperature as variables (0.5-4h, 150-240 °C), while pressure (3 mbar) and steam flow (1 g water/g oil per hour) were kept constant. The analysis of MOAH in the oil was performed using a fully automated liquid chromatography coupled with two parallel comprehensive two-dimensional gas chromatography systems with flame ionisation and time-of-flight mass spectrometric detection. Response surfaces plotting the MOAH loss according to time and temperature were built for different MOAH fractions. The latter were defined based on the number of aromatic rings (>3 or ≤3) and the number of carbon atoms present (C16-C20, C20-C24, C24-C35, C35-C40). It was found that at 200 °C, compounds < C24, including weakly alkylated triaromatics, could be reduced to below the limit of quantification, while at 230 °C, it was possible to remove >60% of the C24-C35 fraction, including pentaromatics of low alkylation.

Characterization and Performance of Peanut Shells in Caffeine and Triclosan Removal in Batch and Fixed-Bed Column Tests.

Peanut shells' adsorption performance in caffeine and triclosan removal was studied. Peanut shells were analyzed for their chemical composition, morphology, and surface functional groups. Batch adsorption and fixed-bed column experiments were carried out with solutions containing 30 mg/L of caffeine and triclosan. The parameters examined included peanut shell particle size (120-150, 300-600, and 800-2000 µm), adsorbent dose (0.02-60 g/L), contact time (up to 180 min), bed height (4-8 cm), and hydraulic loading rate (2.0 and 4.0 m3/m2-day). After determining the optimal adsorption conditions, kinetics, isotherm, and breakthrough curve models were applied to analyze the experimental data. Peanut shells showed an irregular surface and consisted mainly of polysaccharides (around 70% lignin, cellulose, and hemicellulose), with a specific surface area of 1.7 m2/g and a pore volume of 0.005 cm3/g. The highest removal efficiencies for caffeine (85.6 ± 1.4%) and triclosan (89.3 ± 1.5%) were achieved using the smallest particles and 10.0 and 0.1 g/L doses over 180 and 45 min, respectively. Triclosan showed easier removal compared to caffeine due to its higher lipophilic character. The pseudo-second-order kinetics model provided the best fit with the experimental data, suggesting a chemisorption process between caffeine/triclosan and the adsorbent. Equilibrium data were well-described by the Sips model, with maximum adsorption capacities of 3.3 mg/g and 289.3 mg/g for caffeine and triclosan, respectively. In fixed-bed column adsorption tests, particle size significantly influenced efficiency and hydraulic behavior, with 120-150 µm particles exhibiting the highest adsorption capacity for caffeine (0.72 mg/g) and triclosan (143.44 mg/g), albeit with clogging issues. The experimental data also showed good agreement with the Bohart-Adams, Thomas, and Yoon-Nelson models. Therefore, the findings of this study highlight not only the effective capability of peanut shells to remove caffeine and triclosan but also their versatility as a promising option for water treatment and sanitation applications in different contexts.

Exploration of therapeutic potential and pesticidal activity of Sapindus mukorossi by In vitro and Insilico profiling of phytochemicals

Sapindus mukorossi popularly known as soap nuts, belongs to the Sapindaceae family and contains 6–10 % of its weight in saponins. These natural soap-nuts have been used for centuries as a natural and eco-friendly alternative to conventional laundry detergents and cleaning products as it is rich in saponin and can be composted after use. The aim of this research is to study the potential of natural extracts from soap nuts using in vitro and insilico profiling of phytochemicals. Soxhlet extraction was performed to obtain the phytochemicals from the plant species. Phytochemical analysis, quantitative analysis, antioxidant assay, and foaming tests were carried out to check the presence of various phytochemicals along with their antioxidant properties. Insilico analysis to analyze their molecular structure and compounds to check their drug-likeness and pesticidal properties were performed using PASS studies and SwissADME webtool for finding new applications of soap nut which are still unrevealed. The results confirmed the presence of saponins, terpenoids, flavanoids and alkaloids. The foaming stability was also found to be 90 % which was equivalent to commercial detergents. The total saponin and phenol in extract was quantified as 139.263 ± 1.40 mg QAEs/g extract and 271.153±1.23 mg GAE/g extract respectively. The antioxidant property was estimated to be 109.691 ± 1.87 µmolTE/g DW. Characterization was done using FTIR and GCMS and based on the results the major compounds were analyzed using insilico PASS studies which revealed various beneficial properties of soap nuts like anti bacterial, insecticidal, anti helminthic etc. Moreover The physiochemical properties, lipophilicity and solubility characteristics of the plant compounds analyzed using SwissADME web tool revealed the therapeutic benefits of S. mukorossi.

18F-Labeled dihydropyridines via Hantzsch reaction for positron emission tomography of P-glycoprotein dysfunction

Despite the availability of various 11C-labeled positron emission tomography (PET) tracers for assessing P-glycoprotein (P-gp) function, there are still limitations related to complex metabolism, high lipophilicity, and low baseline uptake. This study aimed to address these issues by exploring a series of customized dihydropyridines (DHPs) with enhanced stability and reduced lipophilicity as alternative PET tracers for P-gp dysfunction. Compared with verapamil and the rest DHPs, dimethyl 4-(4-fluorophenyl)-2,6-dimethyl-1,4-dihydropyridine-3,5-dicarboxylate (1) exhibited superior cellular uptake differences between the human gastric cancer cell line SGC7901 and its drug-resistant counterpart. [18F]1 is successfully synthesized using a novel “hot-Hantzsch” approach in 22.1 ± 0.1 % radiochemical yields. MicroPET/CT imaging demonstrated that the uptake of [18F]1 in the brains of P-gp blocked mice increased by > 3 times compared to the control group. Additionally, [18F]1 displayed favorable lipophilicity (log D = 2.3) and excellent clearance characteristics, making it a promising tracer candidate with low background noise and high contrast.

Lignin and Pluronic-based nanomicelles as promising amiodarone nanocarriers: Synthesis, physical characterization, biological, and in silico evaluations

Lignin, a major component of herbaceous plants, is one of the most abundant natural poly-mers that has lipophilic character and antipathogenic properties. Another biocompatible polymer is Pluronic F127, that can cross the blood brain barrier (BBB). Herein, novel drug delivery nanosystems based on oil-in-water microemulsions made of these two biocompatible polymers were developed to load amiodarone (AM), a cationic amphipathic drug used for treating cardiac arrhythmia that displays antifungal and antibacterial properties. The use of drug delivery nanocarriers enhances the solubilization and controlled release of this medication, thus reducing its therapeutic dosage and associated side effects. The morphology, size and surface charge of the nanomiceles was characterized via scanning and transmission electron microscopy (SEM and TEM), dynamic light scattering (DLS) and zeta potential measurements, respectively, which demonstrated their spherical shape, with an average diameter of 27 nm and a zeta potential of −25 mV. Very high entrapment efficiencies were attained for both types of nanomicelles (79.1% and 83.1% for lignin and F127, respectively). Furthermore, both types of AM-loaded nanomicelles exhibited a slower release profile compared to the free drug. Cytotoxicity assay with morphological examination of NIH/3T3 fibroblast cells confirmed a reduction in drug toxicity upon loading onto the nanocarriers. Blood cultures in a chocolate agar medium corroborated that the antibacterial properties of AM are preserved after nanomicelle encapsulation. The interactions of AM with F127 and lignin monomers were investigated via quantum mechanical computations, which revealed the formation of strong hydrogen bonds, the most intense being between AM and lignin. Overall, these novel formulations exhibit great potential for the sustained and targeted AM delivery.

Quantum Chemical-Based Investigations and Lipophilicity Evaluations on Some Structurally Related Quinazoline Derivatives

This work was chiefly conceived to explore the substituent effects on thermodynamic, electronic and lipophilic characteristics of some quinazoline derivatives (Q1-Q4) from theoretical aspects. The variations caused by methyl, ethyl, chlorine and bromine substituents on the same carbon of the aromatic ring were evaluated with a computational approach. In accordance with this purpose, simultaneously, DFT-based calculations were performed for vacuum and two different surroundings (DMSO and water) on methaqualone (Q1), etaqualone (Q2), mecloqualone (Q3), and mebroqualone (Q4) compounds by using the B3LYP functional and 6-311++G(d, p) split-valence triple zeta basis set. The computed thermodynamic quantities revealed that the halogen substitution was more preferable. The effect of substituent modification on electrostatic surface features was evaluated visually by molecular electrostatic potential (MEP) mapping technique. To shed light on the chemical reactivity behaviors of the Q1-Q4, DFT-based reactivity identifiers were computed. Also, the intramolecular interactions affected by substitution were evaluated on the basis of the Natural Bond Orbital (NBO) theory. The NBO results revealed that π-π* interactions predominate for each compound. The lipophilic character analyzes of the mentioned compounds were evaluated both numerically and visually. The data of both methods support each other.

Physical characterization and bioavailability assessment of 5-fluorouracil-based nanostructured lipid carrier (NLC): In vitro drug release, Hemolysis, and permeability modulation.

5-Fluorouracil (5-FU) is an anticancer agent belonging to BCS Class III that exhibits poor release characteristics and low retention in the biological system. The main objective of this investigation was to develop a drug delivery system, i.e., Nanostructure Lipid Carriers (NLCs) loaded with 5-FU to prolong its biological retention through 5-FU-loaded NLCs (5-FUNLC) were designed to manipulate physicochemical characteristics and assessment of in vitroandin vivoperformance. The developed NLCs underwent comprehensive characterization, including assessments for particle size, zeta potential, morphological evaluation, and FT-IR spectroscopy. Additionally, specific evaluations were conducted for 5-FUNLCs, encompassing analyses for encapsulation efficiency of the drug, release characteristics in PBS at pH 6.8, and stability study. The lipophilic character of 5-FUNLC was confirmed through the measurement of the partition coefficient (log P). 5-FUNLCs were observed as spherical-shaped particles with a mean size of 300 ± 25nm. The encapsulation efficiency was determined to be 89%, indicating effective drug loading within the NLCs. Furthermore, these NLCs exhibited a sustained release nature lasting up to 3-4h, indicating their potential for controlled drug release over time. Lipid components were biocompatible with the 5-FU to determine thermal transition temperature and show good stability for 30days. Additionally,an in vitrohemolysis study that confirmed the system did not cause any destruction to the RBCs during intravenous administration. The drug's gut permeability was assessed utilizing the optimized 5-FUNLC (F2) in comparison to 5-FU through the intestine or gut sac model (in the apical to basolateral direction, A → B). The permeability coefficient was measured as 4.91 × 10-5cm/h with a significant difference. Additionally, the antioxidant potential of the NLCs was demonstrated through the DPPH method. The NLCs' performance was further assessed throughin vivopharmacokinetic studies on Wistar Rats, resulting in a 1.5-fold enhancement in their activity compared to free 5-FU. These NLCs offer improved drug solubility and sustained release, which collectively contribute to enhanced therapeutic outcomes and modulate bioavailability. The study concludes by highlighting the potential of 5-FUNLC as an innovative and efficient drug delivery system. The findings suggest that further preclinical investigations are warranted, indicating a promising avenue for the development of more effective and well-tolerated treatments for cancer.

Analysis of vitamin D and its metabolites in biological samples – Part II: Optimization of a sample preparation method for liver tissue

Extraction of vitamin D, including its hydroxylated and esterified metabolites, from soft tissues such as the liver is challenging due to the lipophilic character of matrix and analytes that are expected in very low concentration levels.In this study, we aimed at the optimization of two-step extraction using solid–liquid extraction as the first step, followed by solid-phase extraction. Various solvents, including ethanol, acetonitrile, methanol, acetone, heptane, and heptane with isopropanol, were investigated to isolate vitamin D compounds from liver tissue in the first step. Acetone was finally selected as the most suitable solvent for the solid–liquid extraction, with the highest recovery in the range of 67 – 98% for polar hydroxylated forms and 3 – 28% for lipophilic vitamin D and esters. Two solid phase extraction (SPE) based on the (i) “bind and elute strategy” and (ii) “removal strategy” using hydrophilic-lipophilic balanced SPE sorbent were optimized as a proceeding step for acetone extracts to increase the method selectivity. Finally, two optimized methods, combining solid–liquid extraction and individual SPE strategy, were examined in terms of sensitivity, recovery, matrix effect, accuracy, and precision.The limits of quantification were in the range of 1 – 10 ng/mL and 3 – 20 ng/mL analyzed by ultra-high performance supercritical fluid chromatography and ultra-high performance liquid chromatography hyphenated a with tandem mass spectrometer, respectively. The absolute recovery determined for the “bind and elute strategy” protocol was in the range of 3 – 24 %. Nevertheless, this method was free of matrix effects, which were determined to be in the 73 – 120 % range. On the contrary, the “removal strategy” approach provided higher recovery values for all compounds (47 – 123 %), but the results for nonpolar vitamin D and esters were strongly affected by signal suppression (matrix effects 3 – 51 %). Both methods fulfilled the criteria for accuracy and precision requested by the European Medicine Agency Guideline on Bioanalysis.“Removal strategy” SPE with decreased manual intervention and lower solvent consumption was finally applied to mouse liver tissue to determine vitamin D and its hydroxylated and esterified metabolites for the first time. The results, i.e., vitamin D esters detected in liver tissue, supported the notion that esters of vitamin D can be stored in lipophilic tissues to release vitamin D.

Evaluation of Nanoparticles Covalently Bound with BODIPY for Their Photodynamic Therapy Applicability.

Photodynamic therapy (PDT) relies on the combined action of a photosensitizer (PS), light at an appropriate wavelength, and oxygen, to produce reactive oxygen species (ROS) that lead to cell death. However, this therapeutic modality presents some limitations, such as the poor water solubility of PSs and their limited selectivity. To overcome these problems, research has exploited nanoparticles (NPs). This project aimed to synthesize a PS, belonging to the BODIPY family, covalently link it to two NPs that differ in their lipophilic character, and then evaluate their photodynamic activity on SKOV3 and MCF7 tumor cell lines. Physicochemical analyses demonstrated that both NPs are suitable for PDT, as they are resistant to photobleaching and have good singlet oxygen (1O2) production. In vitro biological analyses showed that BODIPY has greater photodynamic activity in the free form than its NP-bounded counterpart, probably due to greater cellular uptake. To evaluate the main mechanisms involved in PDT-induced cell death, flow cytometric analyses were performed and showed that free BODIPY mainly induced necrosis, while once bound to NP, it seemed to prefer apoptosis. A scratch wound healing test indicated that all compounds partially inhibited cellular migration of SKOV3 cells.