Novel synthesized ionizable lipid for LNP-mediated P2X7siRNA to inhibit migration and induce apoptosis of breast cancer cells.

The development of ionizable lipid (IL) was necessary to enable the effective formulation of small interfering RNA (siRNA) to inhibit P2X7 receptors (P2X7R), a key player in tumor proliferation, apoptosis, and metastasis. In this way, the synthesis and utility of IL for enhancing cellular uptake of lipid nanoparticles (LNP) improve the proper delivery of siRNA-LNPs for knockdown overexpression of P2X7R. Therefore, to evaluate the impact of P2X7 knockdown on breast cancer (BC) migration and apoptosis, a branched and synthesized ionizable lipid (SIL) was performed for efficient transfection of LNP with siRNA for targeting P2X7 receptors (siP2X7) in mouse 4T-1 cells. Following synthesis and structural analysis of SIL, excellent characterization of the LNP was achieved (Z-average 126.8 nm, zeta-potential - 12.33, PDI 0.16, and encapsulation efficiency 85.35%). Afterward, the stability of the LNP was evaluated through an analysis of the leftover composition, and toxic concentration values for SIL and siP2X7 were determined. Furthermore, siP2X7-LNP cellular uptake in the formulation was assessed via confocal microscopy. Following determining the optimal dose (45 pmol), wound healing analysis was assessed using scratch assay microscopy, and apoptosis was evaluated using flow cytometry. The use of the innovative branched SIL in the formulation of siP2X7-LNP resulted in significant inhibition of migration and induction of apoptosis in 4T-1 cells due to improved cellular uptake. Subsequently, the innovative SIL represents a critical role in efficiently delivering siRNA against murine triple-negative breast cancer cells (TNBC) using LNP formulation, resulting in significant efficacy.

Solubility and thermodynamics of mesalazine in aqueous mixtures of poly ethylene glycol 200/600 at 293.2-313.2K.

In this study, the solubility of mesalazine was investigated in binary solvent mixtures of poly ethylene glycols 200/600 and water at temperatures ranging from 293.2K to 313.2K. The solubility of mesalazine was determined using a shake-flask method, and its concentrations were measured using a UV-Vis spectrophotometer. The obtained solubility data were analyzed using mathematical models including the van't Hoff, Jouyban-Acree, Jouyban-Acree-van't Hoff, mixture response surface, and modified Wilson models. The experimental data obtained for mesalazine dissolution encompassed various thermodynamic properties, including ΔG°, ΔH°, ΔS°, and TΔS°. These properties offer valuable insights into the energetic aspects of the dissolution process and were calculated based on the van't Hoff equation.

Solubility and thermodynamics properties of salicylic acid in binary mixtures 1-propanol and propylene glycol/ethylene glycol monomethyl ether at different temperatures.

The research aimed to investigate the solubility and thermodynamics of salicylic acid in two binary solvent mixtures of (1-propanol+propylene glycol) and (ethylene glycol monomethyl ether+1-propanol). The study was conducted in the temperature range of 293.2 to 313.2K. To analyze the experimental solubility data, several linear and nonlinear cosolvency models, such as the van't Hoff, Jouyban-Acree, Jouyban-Acree-van't Hoff, mixture response surface, and modified Wilson models were employed. The models' effectiveness was evaluated by comparing the mean relative deviations of the back-calculated solubility data to the experimental values. In addition, the apparent thermodynamic parameters, including Gibbs energy, enthalpy, and entropy, were calculated using the van't Hoff and Gibbs equations. Furthermore, the study measured the density values for salicylic acid-saturated mixtures and represented them mathematically through the Jouyban-Acree model.

Pharmacological interaction and immune response of purinergic receptors in therapeutic modulation.

Nucleosides and purine nucleotides serve as transmitter and modulator agents that extend their functions beyond the cell. In this context, purinergic signaling plays a crucial role in regulating energy homeostasis and modulating metabolic alterations in tumor cells. Therefore, it is essential to consider the pharmacological targeting of purinergic receptors (PUR), which encompass the expression and inhibition of P1 receptors (metabotropic adenosine receptors) as well as P2 receptors (extracellular ATP/ADP) comprising P2X and P2Y receptors. Thus, the pharmacological interaction between inhibitors (such as RNA, monoclonal antibodies, and small molecules) and PUR represents a key aspect in facilitating the development of therapeutic interventions. Moreover, this review explores recent advancements in pharmacological inhibitors and the regulation of innate and adaptive immunity of PUR, specifically in relation to immunological and inflammatory responses. These responses encompass the release of pro-inflammatory cytokines (PIC), the production of reactive oxygen and nitrogen species (ROS and RNS), the regulation of T cells, and the activation of inflammasomes in all human leukocytes.

Design, Synthesis, and Biological Evaluation of Novel Indanone Derivatives as Cholinesterase Inhibitors for Potential Use in Alzheimer's Disease.

Indanone derivatives containing meta/para-substituted aminopropoxy benzyl/benzylidene moieties were designed based on the structures of donepezil and ebselen analogs as the cholinesterase inhibitors. The designed compounds were synthesized and their acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) inhibitory activities were measured. Inhibitory potencies (IC50 values) for the synthesized compounds ranged from 0.12 to 11.92 µM and 0.04 to 24.36 µM against AChE and BChE, respectively. Compound 5 c showed the highest AChE inhibitory potency with IC50 value of 0.12 µM, whereas the highest BChE inhibition was achieved by structure 7 b (IC50 =0.04 µM). Structure-activity relationship (SAR) analysis revealed that there is no significant difference between meta and para-substituted derivatives in AChE and BChE inhibition. However, the most potent AChE inhibitor 5 c belongs to meta-substituted compounds, while the most active BChE inhibitor is para-substituted derivative 7 b. The order of enzyme inhibition potency based on the substituted amine group is dimethyl amine>piperidine>morpholine. Compounds containing C=C linkage are more potent AChE inhibitors than the corresponding saturated structures. Molecular docking studies indicated that 5 c interacts with AChE in a very similar way to that observed experimentally for donepezil. The introduced indanone-aminopropoxy benzylidenes could be used in drug-discovery against Alzheimer's disease.

Development of New Inhibitors of HDAC1-3 Enzymes Aided by In Silico Design Strategies.

Histone deacetylases (HDACs) are overexpressed in cancer, and their inhibition shows promising results in cancer therapy. In particular, selective class I HDAC inhibitors such as entinostat are proposed to be more beneficial in breast cancer treatment. Computational drug design is an inevitable part of today's drug discovery projects because of its unequivocal role in saving time and cost. Using three HDAC inhibitors trichostatin, vorinostat, and entinostat as template structures and a diverse fragment library, all synthetically accessible compounds thereof (∼3200) were generated virtually and filtered based on similarity against the templates and PAINS removal. The 298 selected structures were docked into the active site of HDAC I and ranked using a calculated binding affinity. Top-ranking structures were inspected manually, and, considering the ease of synthesis and drug-likeness, two new structures (3a and 3b) were proposed for synthesis and biological evaluation. The synthesized compounds were purified to a degree of more than 95% and structurally verified using various methods. The designed compounds 3a and 3b showed 65-80 and 5% inhibition on HDAC 1, 2, and 3 isoforms at a concentration of 10 µM, respectively. The novel compound 3a may be used as a lead structure for designing new HDAC inhibitors.

Changes of body composition and circulating neopterin, omentin-1, and chemerin in response to thylakoid-rich spinach extract with a hypocaloric diet in obese women with polycystic ovary syndrome: A randomized controlled trial.

This trial evaluated the effects of thylakoid-rich spinach extract supplementation combined with a hypocaloric diet on body composition and serum levels of neopterin, chemerin, and omentin-1 in obese women with polycystic ovary syndrome (PCOS). In this randomized controlled trial, 48 obese women with PCOS, aged 20-45 years old, were recruited and randomly divided into thylakoid (n = 24) and placebo (n = 24) groups. They received a low-calorie diet with 5 g/day thylakoid-rich spinach extract or a low-calorie diet with 5 g/day placebo for 12 weeks. The mean age of the participants of the thylakoid group was 31.86 years, and the placebo group was 32.04 years. Thylakoid-rich spinach extract supplementation with a low-calorie diet increased serum levels of omentin-1 (10.90 vs. 3.87 ng/L; p < .001) and decreased fat mass (-5.19 vs. -1.35 kg; p < .001) and serum levels of neopterin (-0.66 vs. -0.38 nmol/L; p = .003) and chemerin (-41.24 vs. -11.26 ng/L; p < .001) in the thylakoid group compared to the placebo group. A significant improvement in omentin-1, chemerin, and neopterin by thylakoid-rich spinach extract supplementation was under the influence of weight change and insulin resistance status throughout the study. A significant decrease in the other anthropometric indices and insulin resistance was also observed in the thylakoid group, compared to the placebo group (p < .001, for all parameters). Thylakoid-rich spinach extract combined with a low-calorie diet increased circulating omentin-1 and decreased fat mass, abdominal obesity, as well as circulating chemerin, neopterin, and insulin in obese women with PCOS.

Synthesis and Biological Evaluation of 1,3,5-Trisubstituted 2-Pyrazolines as Novel Cyclooxygenase-2 Inhibitors with Antiproliferative Activity.

A new series of 1,3,5-trisubstituted 2-pyrazolines for the inhibition of cyclooxygenase-2 (COX-2) were synthesized. The designed structures include a COX-2 pharmacophore SO2 CH3 at the para-position of the phenyl ring located at C-5 of a pyrazoline scaffold. The synthesized compounds were tested for in vitro COX-1/COX-2 inhibition and cell toxicity against human colorectal adenocarcinoma cell lines HT-29. The lead compound (4-chlorophenyl){5-[4-(methanesulfonyl)phenyl]-3-phenyl-4,5-dihydro-1H-pyrazol-1-yl}methanone (16) showed significant COX-2 inhibition (IC50 =0.05±0.01 µM), and antiproliferative activity (IC50 =5.46±4.71 µM). Molecular docking studies showed that new pyrazoline-based compounds interact via multiple hydrophobic and hydrogen-bond interactions with key binding site residues of the COX-2 enzyme.

Hybridization-based design of novel anticholinesterase indanone-carbamates for Alzheimer's disease: Synthesis, biological evaluation, and docking studies.

Inspired by the structures of donepezil and rivastigmine, a novel series of indanone-carbamate hybrids was synthesized using the pharmacophore hybridization-based design strategy, and their biological activities toward acetylcholinesterase (AChE) and butyrylcholinesterase were evaluated. Among the synthesized compounds, 4d and 4b showed the highest AChE inhibitory activities with IC50 values in the micromolar range (compound 4d: IC50 = 3.04 µM; compound 4b: IC50 = 4.64 µM). Moreover, the results of the Aß1-40 aggregation assay revealed that compound 4b is a potent Aß1-40 aggregation inhibitor. The kinetics of AChE enzymatic activity in the presence of 4b was investigated, and the results were indicative of a reversible partial noncompetitive type of inhibition. A molecular docking study was conducted to determine the possible allosteric binding mode of 4b with the enzyme. The allosteric nature of AChE inhibition by these compounds provides the opportunity for the design of subtype-selective enzyme inhibitors. The presented indanone-carbamate scaffold can be structurally modified and optimized through medicinal chemistry-based approaches for designing novel multitargeted anti-Alzheimer agents.

The effects of spinach-derived thylakoid supplementation in combination with calorie restriction on anthropometric parameters and metabolic profiles in obese women with polycystic ovary syndrome: a randomized, double-blind, placebo-controlled clinical trial.

BACKGROUND: There is a promising outlook regarding the potential effect of spinach-derived thylakoids in the management of obesity and its associated metabolic disturbances. This research aimed to evaluate the effects of spinach-derived thylakoids supplementation combined with a calorie-restricted diet on anthropometric and metabolic profiles in obese women with the polycystic ovary syndrome (PCOS). METHODS: In a 12-week double-blind placebo-controlled randomized clinical trial, 48 females with obesity and PCOS were randomly allocated into either intervention (5 g/day thylakoid) or placebo (5 g/day cornstarch) groups along with calorie-restricted diets. Anthropometric measures, physical activity levels, dietary intakes, insulin resistance markers, as well as serum levels of insulin, fasting blood glucose (FBG), non-esterified fatty acids (NEFA), and sex hormones including dehydroepiandrosterone sulfate (DHEAS), follicle-stimulating hormone (FSH), luteinizing hormone (LH), sex hormone-binding globulin (SHBG), and free androgen index (FAI) were evaluated pre-and post-intervention. RESULTS: After the 12-week intervention, there were significant decreases in weight (- 6.97 ± 0.52 vs. -3.19 ± 0.72 kg; P < 0.001), waist circumference (- 7.78 ± 2.50 vs. -3.73 ± 1.40 cm; P < 0.001), fat mass (- 5.19 ± 0.53 vs. -1.36 ± 0.39 kg; P < 0.001), and insulin levels (- 5.40 ± 1.86 vs. -1.19 ± 0.85 µU/mL; P < 0.001) in the spinach-derived thylakoid group compared to the placebo group. Furthermore, insulin resistance markers and serum levels of testosterone decreased significantly in the thylakoid group compared to the placebo group (P < 0.05). The changes in other parameters did not show significant differences between the two groups. CONCLUSIONS: Spinach-derived thylakoid supplementation resulted in more favorable improvements in anthropometric indices and insulin sensitivity compared to the calorie restriction alone. TRIAL REGISTRATION: The study was approved by the Ethics Committee of Research Vice-chancellor of Tabriz University of Medical Sciences, Tabriz, Iran, and was registered in the Iranian Registry of Clinical Trials (registration ID: IRCT20140907019082N9 ).

Synthesis of a novel superdisintegrant by starch derivatization with polysuccinimide and its application for the development of Ondansetron fast dissolving tablet.

CONTEXT: Disintegrants are the key excipients administered in tablet formulations to boost the decomposition of the tablet into smaller pieces in the gastrointestinal environment, thereby increasing the available surface area and enhancing a more rapid release of the active ingredient. OBJECTIVE: Polysuccinimide (PSI), a biodegradable polymer synthesized from aspartic acid, was reacted with starch and fully assessed by CHN, 1H-NMR, and FTIR. METHODS: PSI-grafted starch (PSI-St) was synthesized and applied as a disintegrant in the formulation of a rapidly disintegrating tablet of Ondansetron, a nausea and vomiting medicine. The tablet formulated with the newly developed superdisintegrant was evaluated for hardness, friability, disintegration time, and dissolution rate, and the results were compared with tablets formulated with an identical composition of test formulation differing only in type of disintegrant. RESULTS: Tablets prepared with starch and tablets prepared with sodium starch glycolate (SSG) were used as negative and positive controls, respectively. Dissolution study results indicated that although the onset of disintegration action was faster for SSG than PSI-St, higher amounts of drug were released from tablets formulated from PSI-St than from those formulated from SSG during 10 min. CONCLUSION: It was concluded that the novel synthesized superdisintegrant has an appropriate potential for the application in the formulation of fast dissolving tablets.

Synthesis of a novel superdisintegrant by starch derivatization with polysuccinimide and its application for the development of Ondansetron fast dissolving tablet.

CONTEXT: Disintegrants are the key excipients administered in tablet formulations to boost the decomposition of the tablet into smaller pieces in the gastrointestinal environment, thereby increasing the available surface area and enhancing a more rapid release of the active ingredient. OBJECTIVE: Polysuccinimide (PSI), a biodegradable polymer synthesized from aspartic acid, was reacted with starch and fully assessed by CHN, (1)H-NMR, and FTIR. METHODS: PSI-grafted starch (PSI-St) was synthesized and applied as a disintegrant in the formulation of a rapidly disintegrating tablet of Ondansetron, a nausea and vomiting medicine. The tablet formulated with the newly developed superdisintegrant was evaluated for hardness, friability, disintegration time, and dissolution rate, and the results were compared with tablets formulated with an identical composition of test formulation differing only in type of disintegrant. RESULTS: Tablets prepared with starch and tablets prepared with sodium starch glycolate (SSG) were used as negative and positive controls, respectively. Dissolution study results indicated that although the onset of disintegration action was faster for SSG than PSI-St, higher amounts of drug were released from tablets formulated from PSI-St than from those formulated from SSG during 10 min. CONCLUSION: It was concluded that the novel synthesized superdisintegrant has an appropriate potential for the application in the formulation of fast dissolving tablets.

Effects of Pomegranate (Punica granatum L.) Peel Extract Supplementation on Markers of Inflammation and Serum Matrix Metalloproteinase 1 in Women With Knee Osteoarthritis: A Randomized Double-Blind Placebo-Controlled Study.

Objective: Osteoarthritis (OA) as a common musculoskeletal disorder is the main cause of disability in the world. The present study aimed to evaluate the effects of pomegranate peel extract (PPE) on some inflammatory markers and matrix maloproteinase1 (MMP1) in women with knee OA. Methods: Sixty obese women with knee OA aged 38 to 60 years were included in this clinical trial. The women were allocated into intervention (n = 30) and placebo (n = 30) groups along with standard drug therapy receiving 500 mg PPE or placebo twice daily for 8 weeks, respectively. Three-day food records, anthropometric measurements, fasting blood samples, and physical activity questionnaires were gathered at the baseline and the end of the study. Results: The supplementation of PPE significantly reduced the serum high-sensitivity C-reactive protein (hs-CRP), nuclear factor kappa-light-chain-enhancer of activated B cells (NF-ĸB), MMP1, and monocyte chemoattractant protein-1 (MCP-1) levels of the patients within the intervened group (all, P < .05) and compared with the placebo (P = .002, .045, .040, and .003, respectively) at the end of the study. The serum NF-ĸB levels significantly increased within the placebo group at the end of the trial (P = .002). Changes in other variables in the placebo group were not significant (P > .05). Conclusions: The findings of this clinical trial indicated that PPE supplementation decreased serum inflammatory markers including hs-CRP, NF-ĸB, and MCP-1 and MMP1 levels in women with knee OA. PPE supplementation may be useful as a part of an integrated approach to modulating inflammatory complications in women with knee OA.

Effects of chitosan and TiO2 nanoparticles on the antibacterial property and ability to self-healing of cracks and retrieve mechanical characteristics of dental composites.

The aim of this study was to improve the self-healing properties of dental nanocomposite using nanoparticles of TiO2 and chitosan. We evaluated flexural and compressive strength, crack-healing, and self-healing lifespan after 3 months of water aging. The effect of the developed composite on cell viability and toxicity was assessed by an MTT assay on human alveolar basal epithelial cells (A549 cell line). The nanocomposite included 7.5 wt% polyurea-formaldehyde (PUF) and 0, 0.5, and 1 wt% n-TiO2 and chitosan. After the fracture, the samples were put in a mold for 1-90 days to enable healing. Then, the fracture toughness of the healed nanocomposites and the healing yield were measured. The flexural strength of the nanocomposite improved by adding 0.5 wt% n-TiO2, while the compressive strength increased after adding 0.5 wt% chitosan (p > 0.1). When these two materials were used simultaneously, the flexural strength was improved by around 2%; however, the compressive strength was unaffected. Compared to the other sample, the nanocomposite with 0.5 wt% n-TiO2 and chitosan had higher KIC-healing and self-healing efficiency. Self-healing efficacy had no significant effect of water aging over 90 days compared to one day (p > 0.1), demonstrating that the PUF nanocapsules were not damaged.

Investigation of the solubility and thermodynamics of salicylic acid in 2-propanol and ethylene glycol/propylene glycol binary solvent mixtures at (293.15 to 313.15) K.

This study aimed to measure both the solubility and thermodynamics of salicylic acid in binary solvent mixtures of (2-propanol + ethylene glycol) and (2-propanol + propylene glycol) at different temperatures in the range of 293.2-313.2 K. The experimental solubility data were analyzed using various linear and nonlinear cosolvency models, such as the van'tt Hoff, Jouyban-Acree, Jouyban-Acree-van'tt Hoff, mixture response surface and modified Wilson models and to evaluate the models, the mean relative deviations of the back-calculated solubility data were compared with experimental values. Through this analysis, the apparent thermodynamic parameters, including Gibbs energy, enthalpy, and entropy were calculated using the van'tt Hoff and Gibbs equations for this system. Additionally, the density values for salicylic acid saturated mixtures were also measured and represent mathematically using the Jouyban-Acree model.

Enhanced intracellular accumulation and cytotoxicity of bortezomib against liver cancer cells using N-stearyl lactobionamide surface modified solid lipid nanoparticles.

Asialoglycoprotein receptors (ASGPRs) are highly expressed on hepatocytes and have been used for liver-targeted delivery and hepatocellular carcinoma (HCC) therapy. However, targeted delivery of bortezomib (BTZ) to HCC has not been reported. In this study, N-stearyl lactobionamide (N-SALB) with galactose (Gal) moiety was synthesized as a targeting agent and its structure was confirmed by FT-IR and NMR analyses. N-SALB surface-modified solid lipid nanoparticles (SLNs) loaded with BTZ (Gal-SLNs/BTZ) were developed to target BTZ delivery into HCC cancer cells. The Gal-SLNs/BTZ had an average particle size of 116.3 nm, polydispersity index (PDI) of 0.210, and zeta potential of -13.8 mV. TEM analysis showed their nanometer-sized spherical morphology. The encapsulation efficiency (EE) and drug loading (DL) capacity were 84.5 % and 1.16 %, respectively. Release studies showed that BTZ loaded inside the SLNs was slowly released over a period of 72 h at pH 7.4. Flow cytometry analysis showed significantly higher intracellular uptake of N-SALB-targeted nanoparticles than non-targeted nanoparticles in HepG2 cells. All lipid formulations showed good biocompatibility in the cytotoxicity study using MTT assay. Concentration-dependent cytotoxicity was observed for all formulations, with N-SALB-targeted nanoparticles demonstrating more cytotoxicity against HepG2 cells. The highest percentage of apoptosis was obtained for N-SALB-targeted nanoparticles compared to non-targeted nanoparticles (42.2 % and 8.70 %, respectively). Finally, biodistribution studies in HepG2 bearing nude mice showed that the accumulation of targeted nanoparticles in the tumor was significantly higher than non-targeted nanoparticles.

Key structural requirements of benzamide derivatives for histone deacetylase inhibition: design, synthesis and biological evaluation.

Background: Histone deacetylase inhibitors (HDACIs) are important as anticancer agents. Objective: This study aimed to investigate some key structural features of HDACIs via the design, synthesis and biological evaluation of novel benzamide-based derivatives. Methods: Novel structures, designed using a molecular modification approach, were synthesized and biologically evaluated. Results: The results indicated that a subset of molecules with CH3/NH2 at R2 position possess selective antiproliferative activity. However, only those with an NH2 group showed HDACI activity. Importantly, the shorter the molecule length, the stronger HDACI. Among all, 7j was the most potent HDAC1-3 inhibitor and antiproliferative compound. Conclusion: The results of the present investigation could provide valuable structural knowledge applicable for the development of the HDACIs and benzamide-based antiproliferative agents in the future.

[Box: see text].

Expression, Purification and Characterization of Functional Teduglutide Using GST Fusion System in Prokaryotic Cells.

Purpose: Teduglutide is the first and only FDA-approved drug for long-term treatment of short bowel syndrome (SBS). The current study aimed to present an approach for production of teduglutide using recombinant DNA technology. Methods: The coding gene for teduglutide was cloned into pGEX-2T vector, where coding sequence for factor Xa cleavage site was added between GST and teduglutide coding genes. The GST-teduglutide protein was overexpressed in E. coli BL21 (DE3) strain and affinity purified using glutathione sepharose affinity column. Results: On-column proteolytic activity of factor Xa followed by size exclusion chromatography resulted in the pure teduglutide. Circular dichroism (CD) spectropolarimetry showed that the produced teduglutide folds into mainly α-helical structure (>50%), as expected. In mass spectroscopy analysis, the fragments of teduglutide resulted by cyanogen bromide cleavage as well as those expected theoretically due to mass fragmentation were identified. The functionality of the produced peptide was evaluated by measuring its proliferative effect on Caco2 intestinal epithelial cells, and the results indicated that produced teduglutide induces cell proliferation by 19±0.30 and 33±7.82 % at 1.21 and 3.64 µM concentrations, respectively, compared to untreated cells. Conclusion: Teduglutide was successfully expressed and purified and its functionality and structural integrity were confirmed by in vitro experiments. We believe that the experimental-scale method presented in the current study can be useful for pilot-scale and also industrial-scale production of teduglutide.

A Modified Electrochemical Sensor Based on N,S-Doped Carbon Dots/Carbon Nanotube-Poly(Amidoamine) Dendrimer Hybrids for Imatinib Mesylate Determination.

Imatinib mesylate, an anticancer drug, is prescribed to treat gastrointestinal stromal tumors and chronic myelogenous leukemia. A hybrid nanocomposite of N,S-doped carbon dots/carbon nanotube-poly(amidoamine) dendrimer (N,S-CDs/CNTD) was successfully synthesized and used as a significant modifier to design a new and highly selective electrochemical sensor for the determination of imatinib mesylate. A rigorous study with electrochemical techniques, such as cyclic voltammetry and differential pulse voltammetry, was performed to elucidate the electrocatalytic properties of the as-prepared nanocomposite and the preparation procedure of the modified glassy carbon electrode (GCE). A higher oxidation peak current was generated for the imatinib mesylate on a N,S-CDs/CNTD/GCE surface compared to the GCE and CNTD/GCE. The N,S-CDs/CNTD/GCE showed a linear relationship between the concentration and oxidation peak current of the imatinib mesylate in 0.01-100 µM, with a detection limit of 3 nM. Finally, the imatinib mesylate's quantification in blood-serum samples was successfully performed. The N,S-CDs/CNTD/GCE's reproducibility and stability were indeed excellent.

Synthesis of Novel Cationic Photosensitizers Derived from Chlorin for Application in Photodynamic Therapy of Cancer.

BACKGROUND: Chlorins (dihydroporphyrins) are tetrapyrrole-based compounds that are more effective in photodynamic therapy than porphyrins. The instability of the compounds and their oxidation to porphyrin limits the use of these compounds. However, the design and synthesis of new stable chlorin-based cationic photosensitizers with the potential for use in cancer photodynamic therapy can be interesting. METHODS: In this research, new tetracationic meso substituted chlorins were designed, synthesized, and characterized. After determining the chemical structure and spectroscopic properties of five new photosensitizers, their phototoxicity on breast cancer cell lines (MCF-7) was investigated under optimized conditions in terms of factors such as photosensitizer concentrations and light intensity. RESULTS: The results of cytotoxicity assayed by the MTT method showed that the synthesized compounds, even up to the concentration of 50 µM had very low toxicity in the absence of light, which indicates their safety under dark conditions. Compounds A1 and A3 with the best physicochemical properties such as solubility, high absorption intensity in the effective range of photodynamic therapy, and the high quantum yield of singlet oxygen, had a good toxic effect (IC50 = 0.5 µM) on the cancer cells (MCF-7) in the presence of laser light. CONCLUSION: According to the obtained results, compounds A1 and A3 have the potential to continue research on PDT for confirmation and use in treatment.