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Optimization and Synthesis of Perfluorocarbon Nanoemulsion with Fluorous Photosensitizer for Photodynamic Therapy

Perfluorocarbon-based nanoemulsions (PFC-NEs) have been shown to be an effective tool for oxygen delivery in various therapeutic modalities, including photodynamic therapy (PDT) in cancer treatment. PFC droplets are able to transport and supply oxygen to hypoxic cells as well as enhance the singlet oxygen generation by the photosensitizer (PS), functions which make them a promising platform for PDT. To further enhance PDT efficacy, we synthesized PFC-NEs with fluorous PS that is soluble in the perfluorocarbon phase, creating a closer proximity of the PS to the dissolved oxygen in PFC. However, the fluorous PS used in this work had a high tendency to leak into the aqueous phase with a surfactant, leading to less than desirable encapsulation efficiency (EE%). Therefore, the main goal of this study is to develop a formulation to ensure high EE% of fluorous PS in PFC droplets. PFC-NEs were prepared by ultrasonic emulsification and were characterized using dynamic light scattering, UV-Vis and fluorescence spectroscopy. The optimization of the PFC-NE formulation did not significantly affect the nanoemulsion properties, such as hydrodynamic diameter, polydispersity index and colloidal stability, and successfully increased EE%, as well as improved dark cytotoxicity profile and enhanced photoinduced cytotoxicity of PFC-NE.

The study was carried out using the equipment of the Core Facility “New Materials and Technologies” at the Emanuel Institute of Biochemical Physics, Russian Academy of Sciences.

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Evaluation of advanced glycation end product and antibodies against oxidized low-density lipoproteins levels in patients with neuroendocrine tumors based on tumor location
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Published: 01 November 2023 by MDPI in 9th International Electronic Conference on Medicinal Chemistry session General

Neuroendocrine neoplasms (NENs) are recognized as a heterogeneous group of tumors derived from neuroendocrine cells present in multiple organ systems. The importance of early and precise detection of NENs for effective treatment outcomes is well-understood. Biochemical markers such as antibodies against oxidatively modified low-density lipoproteins (anti-oxLDLs) and advanced glycation end products (AGEs) could be correlated with the presence and type of these tumors.In this study, an attempt was made to assess the levels of anti-oxLDLs and AGEs in patients diagnosed with NENs, with a tumors located in the lung and pancreas. A total of 20 patients were studied, equally divided between pancreatic NENs (P-NENs) and lung NENs (L-NENs). Venous blood samples from these patients were collected and processed to obtain serum. The levels of anti-ox-LDLs and AGEs were then quantified using the enzyme-linked immunosorbent assay (ELISA) technique. Results were presented as mean values with the standard error of the mean (SEM), and a p-value of less than 0.05 was considered to denote statistical significance. In the findings, anti-oxLDL levels in the P-NEN group were found to average at 6649.000 ± 1445.922 U/mL, while those in the L-NEN group were 5283.000 ± 1016.513 U/mL. A significant difference between these groups was not observed. On the other hand, a significant variation in AGE concentrations was noted: 898.509 ± 27.382 ng/mL for P-NEN patients compared to 763.106 ± 55.143 ng/mL for L-NEN patients. In conclusion, this preliminary findings suggest that AGE concentrations could be a potential biomarker for distinguishing between pancreatic and lung NENs.

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Study of cytotoxicity of spirosubstituted with acenaphthylen-1(2H)-one and aceanthrylen-1(2H)-one fragments cyclopropa[a]pyrrolizidines and 3-azabicyclo[3.1.0]hexanes against tumor cell lines

Oncological diseases are one of the most common public health problems and second leading cause of death after cardiovascular disease. Natural products or synthetic compounds inspired from natural products continue to be excellent sources for new drug candidates. Pyrrolizidines and 3-azabicyclo[3.1.0]hexanes are important classes of heterocyclic compounds with diverse pharmacological activities including anticancer activity. Here we report study of cytotoxicity of newly developed spirosubstituted with acenaphthylen-1(2H)-one and aceanthrylen-1(2H)-one fragments cyclopropa[a]pyrrolizidines and 3-azabicyclo[3.1.0]hexanes against tumor cell lines. The results of antiproliferative activity study showed that spiroadducts with either acenaphthylen-1(2H)-one or aceanthrylen-1(2H)-one framework have shown significant activity with IC50 up to 1 μg/mL. Confocal microscopy study showed diffuse distribution of granular actin in the cell cytoplasm with disappearance of actin filaments. Number of cells with filopodium-like membrane protrusions was also reduced after treatment with some of tested compounds. The obtained results support the antitumor effect of the studied compounds.

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Exploring the Antimicrobial and Antioxidant Potential of Blueberry Leaves in Dermatology
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Blueberries are popular all over the world due to their flavorsome fruit, abundance of bioactive compounds, and antioxidant activity. However, many countries discard large quantities of leaves, so exploiting the bioactive compounds in the leaves would be very beneficial for the agricultural industry. Studies on these residues that identify phytochemicals and evaluate their biological effects have recently been conducted in our group (ref)Therefore, this study highlights the applications of blueberry leaves, focusing on their dermatological, antioxidant, antimicrobial, and antibiofilm activities. The aim was to assess the feasibility of using this by-product in the prevention and treatment of skin problems its antimicrobial efficacy against relevant skin pathogens and its ability to prevent biofilm formation. The results reveal remarkable properties: a total antioxidant activity of 84.21%±0.1, a complete inhibition of hyaluronidase (100%), 55.3 ± 4.2% attenuation of elastase, and 61.2 ± 10.5% suppression of tyrosinase. The antibiofilm results also show substantial inhibitory effects, with a mass quantification inhibition rate of 38% against Cutibacterium acnes and 33% against Staphylococcus aureus, accompanied by a 34% and 48% reversal of their respective metabolic activities. The results obtained indicate that blueberry leaves could be an interesting by-product to be applied as a component of cosmetic and dermatological preparations with antioxidant, antimicrobial, and anti-biofilm properties

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The effects of Lead stress on flavonoid content and antioxidant activity from Scrophularia striata Boiss.
Published: 01 November 2023 by MDPI in 9th International Electronic Conference on Medicinal Chemistry session General

Scrophularia striata Boiss., a local name of Teshnehdari, is used as a common medicinal infusion of the plant aerial parts in hot water. For decades, Teshnehdari has been used in diverse forms, including oral decoction, incense, and poultice for treating various diseases containing eye and ear infections, infectious wounds, colds, and boils. Recently, researchers have recommended applying S. striata for clinical studies on COVID-19 viral illness. One of the reasons for using plants in medicine is the presence of their metabolites and antioxidant activities. Different environmental stresses incredibly affect their antioxidant capacity and medicinal metabolites. The reactive oxygen species (ROS) production often increases in response to heavy metal pollution, especially Pb stress. Plants have a defense system that responds to the imbalance between oxidant and antioxidant activities by increasing antioxidant production. The research purposed to evaluate the effects of Pb stress on the flavonoid content and antioxidant activity of S. striata. The antioxidant activity was distinguished with the evaluation of scavenger enzymes, including guaiacol peroxidase (POD), superoxide dismutase (SOD), and catalase (CAT), using extraction of shoot samples with different collecting times (24, 48, and 72 hours). After 24 h treatment, POD was the predominant antioxidant enzyme and significantly increased compared to control groups. However, SOD and CAT showed a significant increase in modulating the oxidative status at 72h after Pb stress. Statistical analysis showed a negative correlation between POD with CAT and SOD. Based on HPLC analysis of genistein flavonoid, a non-enzymatic antioxidant, meaningfully increased at 24 and 72 h after treatment. Also, Correlation coefficient analysis showed a significant negative relationship between genistein and antioxidant activity (CAT and SOD). Overall, S. striata can be a good source of enzymatic and non-enzymatic antioxidants with application in the pharmaceutical industry.

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Phenolic Compounds as Potential Siderophores

Natural products are a rich source for the design and construction of new biologically or analytically relevant molecules. Multidirectional activity of essential oils (EOs) is widely described in literature: among them antioxidants, antimutagenic, anticarcinogenic, anti-inflammatory, allelopathic, repellent, insecticidal, antiviral, antifungal and antibacterial properties are highlighted. EOs are widely used in food, cosmetic, and pharmaceutical industries.
Many EOs are constituted by phenolic compounds, such as eugenol, thymol and carvacrol, where a presence of hydroxyl group makes them potential siderophores, as a small, high-affinity iron-chelating ligands. Iron acquisition through siderophores is a widely spread strategy among pathogens, in environmental research. For instance, siderophores function as biocontrols, biosensors, and bioremediation and chelation agents.
Considering these facts, the chelation of some EOs are evaluated by UV-vis absorption spectroscopy in relation to various metal cations, as potential ligands.

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Testing Potential Chitosan Hydrogels for 3D Printing
Published: 01 November 2023 by MDPI in 9th International Electronic Conference on Medicinal Chemistry session General

Nowadays 3D printing technology has been rising worldwide, due to its diversity, high customization, and the ability to adapt to different needs, making 3D printing technology a revolutionary approach. This technology can be used in several different fields, including in a healthcare setting. Despite the different types of 3D printing technologies and materials that can be used to print 3D objects, finding the right material and technique to use can be challenging. The materials need to have certain characteristics to be used in humans, and finding the right material for the right technique can be time and cost consuming. Chitosan is a natural polymer and one of the most abundant in nature. It is well known for its non-toxicity and biocompatibility, making this polymer a material of interest for 3D printing in healthcare. The aim of this study is to understand if it is possible to use chitosan-based hydrogels as inks for a 3D printing process and assess which parameters are needed to optimize the process. Chitosan-based hydrogels at different concentrations were produced and used as inks in a 3D extrusion method. An optimization study was conducted to find out which parameters are responsible for optimizing the process. Using the chitosan hydrogels, several scaffolds were printed and evaluated through a visual analysis. The chitosan hydrogels demonstrated potential to be used as inks in a 3D printing process.

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Unveiling the Antimicrobial Properties of Raspberry Leaves Against Multidrug-Resistant Klebsiella pneumoniae
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Klebsiella pneumoniae, a major contributor to nosocomial infections, accounts for 10% of hospital-acquired infections and is classified as a critical and high-priority antibiotic-resistant bacterium by the WHO. Infections stemming from K. pneumoniae are often severe and life-threatening due to high levels of antibiotic resistance, resulting in adverse outcomes. Consequently, there is an urgent need for new drugs effective against K. pneumoniae infections. One promising approach involves exploring the antibacterial potential of natural resources, specifically byproducts rich in bioactive compounds, notably phenolic compounds [1].

In this study, we aimed to assess the antimicrobial, phytochemical, and antioxidant activities of aqueous extracts from raspberry leaves against multidrug-resistant K. pneumoniae strains isolated from clinical wound infections. The results revealed a positive correlation between the phenolic content of raspberry leaves and their antimicrobial efficacy. The findings reveal a total antioxidant activity of 93.5%±0.12. The extracts exhibited antibacterial activity against all K. pneumoniae strains from clinical isolates, with inhibition rates equal to or exceeding 50%. These findings suggest that aqueous extracts of raspberry leaves may serve as a valuable therapeutic resource for combating multi-resistant bacteria.

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7α-acetoxy-6β-hydroxyroyleanone as lead compound: from extraction optimization to hybrid nanoparticles for breast cancer therapy

Breast cancer is the most prevalent cancer worldwide. Plectranthus spp. have been used in traditional medicine for various ailments, including cancer, and its bioactive components have been investigated for their potential anticancer effects. In particular, the compound 7α-acetoxy-6βhydroxyroyleanone (Roy, 1) displayed promising antiproliferative activity against several cancer cell lines. However, Roy 1 is highly hydrophobic and consequently has low water solubility, limiting its therapeutic use. Nanoformulations offer a potential solution. Accordingly, Roy 1 was investigated as a lead compound for the development of new antitumoral drugs through extraction optimization from P. grandidentatus, study of reactivity, evaluation of aqueous stability, and synthesis of Roy 1 gold nanoparticles (NPs). The acetonic ultrasound assisted extraction method was optimized by performing three cycles of 30 minutes each, which improved the isolation yield (46.8 ± 11.25 μg.mg-1). The reactivity of Roy 1 was explored to prepare new bioactive esters. Consequently, a new (4) and three known (2, 3, and 5) ester derivatives were prepared. Considering the stability study, compounds 1, 2, and 3 were evaluated and results indicate that all of them were completely water stable (concentration of 0.1 mM, pH 7.4, and 37°C, for 10 days). Moreover, 1_NPs were successfully synthetized and exhibit promising physicochemical characteristics and an impressive 74.9% drug conjugation efficiency. Additionally, natural 1, derivatives 2-5, and 1_NPs system exhibit significant activity against the aggressive breast cancer cell line, MDA-MB-231. These findings represent a significant advancement in our ongoing efforts to develop novel therapeutic agents and drug delivery platforms.

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Estimation of passive gastrointestinal absorption of selected dual COX-2 and 5-LOX inhibitors using biopartitioning micellar chromatography

Biopartitioning micellar chromatography (BMC) was used to predict passive gastrointestinal absorption of a set of thirteen previously synthesized dual COX-2 and 5-LOX inhibitors. It was performed using ZORBAX Extend-C18 HPLC column (150 mm x 4.6 mm, 5µm). The mobile phase consisted of aqueous phase (40 mmol/l solution of Brij 35 in 7 mmol/l disodium hydrogen phosphate) and acetonitrile (70:30, v/v) and its pH was adjusted to 5.5 by phosphoric acid. The column temperature was set to 36.5 °C, flow rate to 1 ml/min and UV/VIS detection was performed at 240 nm, 254 nm and 400 nm. All tested compounds were injected in duplicates and retention factors (k) were calculated. In addition, effective lipophilicity coefficients (logD) were predicted at pH 5.5 using MarvinSketch 21.4. Retention factors ranged from 0.92 to 36.96. Compound 9 had the lowest k value (0.92), so the lowest passive gastrointestinal absorption can be expected. Low lipophilicity of this compound (logD = - 0.21) is due to the presence of carboxylic acid group, which is ionized at pH 5.5. The most lipophilic compound (13, logD = 5.21) had the highest k value (36.96), so the highest passive gastrointestinal absorption can be expected. The most promising dual COX-2 and 5-LOX inhibitors (1, 2 and 3) had intermediate k and logD values (k: 9.50, 5.55 and 9.33; logD: 2.15, 2.75 and 2.80, respectively). The applied BMC model highlighted compounds with the highest and lowest expected passive gastrointestinal absorption. Obtained results also proved the influence of lipophilicity on BMC retention.

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