Photoactivated chemotherapy is a new strategy for the development of anticancer drugs in which the activity of a chemotherapeutic drug is controlled by light irradiation. This avoids systemic toxicity and reduces side effects. The aim of this work was to evaluate the therapeutic potential of the light-activated prodrug BODIPY-Cab. The tested conjugate consists of cabozantinib, which was used as a cytostatic, and meso-methyl-BODIPY as a photoremovable protecting group (PPG), which is also used as a photosensitizer, allowing for combined therapy.

The photochemical and photophysical properties of the compound were evaluated using a spectrophotometer-spectrofluorometer. To study the biological properties, cell cultures with different expression of target receptors were selected: A-431 (human epidermoid carcinoma), MDA-MB-231 (human breast adenocarcinoma), HEK293 (human embryonic kidney). A laser scanning confocal microscope was used to study the intracellular localization of the BODIPY-Cab. The effect of compounds on cell viability was estimated using the microculture tetrazolium test.

The conjugate has absorption maxima at 368 and 662 nm and a fluorescence maximum at 678 nm. Irradiation of the BODIPY-Cab solution using a red light demonstrated photodegradation of the conjugate and moderate yield of the cabozantinib derivative. Fluorescence quantum yield of BODIPY-Cab was 16%, and the quantum yield of singlet oxygen was 17%. The compound is localized in mitochondria and the endoplasmic reticulum. Activation of the conjugate by light (655−675 nm), increased cytotoxicity, with the generation of ROS, especially superoxide O₂^•−. Cabozantinib derivative exhibited lower toxicity in cells compared to conjugate, suggesting that the photosensitizer should play a predominant role in initiating cellular damage.

The possibility of controlled release of a cytostatic under the action of red light is shown. The results can be used for further optimization of PPG based on meso-methyl-BODIPY.

This work was supported by the Russian Science Foundation under Grant No. 24-13-00179

Introduction. Research interest in orphan drugs has been growing annually. Consequently, new research studies and developments in quality control for this class of medicinal products are required. Given the relevance of this issue, the aim of this study is to investigate the fragmentation mechanism (FM) of the prospidium chloride (PrsCl₂) molecule under electrospray ionization (ESI) to develop new quality control methods using the ESI-HPLC-MS system. Materials and Methods. Prospidium chloride substance (PrsCl₂, Mr=500.3). Orbitrap Exploris 120 mass spectrometer, equipped with a Vanquish liquid chromatograph (Thermo Scientific, USA) and an Acclaim™ RSLC 120 C18 analytical column from Dionex Bonded Silica Products (Thermo Scientific, USA). Sample injection volume: V=5 µL; total analysis time: t=19 minutes. Studies were conducted with aqueous solutions at a concentration of 0.05 mg/mL. Results. The study describes the FM of singly and doubly charged ions formed from the active pharmaceutical ingredient (API): m/z=445,1819 [M – Cl^-]⁺, m/z= 409,2129 [M – 2Cl^- – H⁺]⁺, m/z=205,1101 [M – 2Cl^-]²⁺. However, as demonstrated, these ions may originate not only from the API but also from related impurities. This is critical to consider, as the presence of related impurities may overestimate quantitative analysis results. The study also highlights the FM of ions presumably formed from PrsCl₂ derivative compounds: m/z=373.2365 [M - 3Cl^- - 2H]⁺, m/z=187.1219 [M - 3Cl^- - H]⁺², m/z=169.1336 [M – 4Cl^- - 2H]²⁺. The study results can contribute to the development of a method for determining the purity of the substance.

Conclusion. The demonstrated FM of the PrsCl₂ molecule and its derivatives during chromatographic-mass spectrometric analysis enables the development of methods for qualitative and quantitative analysis, as well as the determination of the purity of the PrsCl₂ substance.

Funding: This research was supported by a grant from the RUDN University Strategic Academic Leadership Programme No. 033320–2-000.

Introduction: Alzheimer's disease (AD) necessitates novel therapeutics. This study aimed to design and develop new heterocyclic cholinesterase inhibitors using a rational, integrated computational and experimental approach, with a focus on achieving potency and selectivity, particularly for butyrylcholinesterase (BuChE).

Methods: Novel piperidine-based analogues were designed via molecular docking simulations against acetylcholinesterase (AChE) and BuChE to predict binding modes. Seven designed compounds were synthesized, and their structures were confirmed using TLC, melting point, UV, IR, EI-MS, and ¹H-NMR. In vitro inhibitory activity was evaluated against both enzymes using the Ellman assay, with donepezil as a reference standard. Drug-likeness was assessed based on Lipinski’s Rule of Five and blood-brain barrier permeability predictions.

Results: Docking studies elucidated a binding mode involving anchoring in the catalytic site and π–π interactions in the peripheral site. In vitro testing identified two potent dual inhibitors, P8 (IC₅₀ = 11.5 µM for BuChE) and P14 (IC₅₀ = 15.3 µM for BuChE), which outperformed donepezil for BuChE inhibition. The series exhibited a selective profile favoring BuChE. Structure-activity relationship (SAR) confirmed terminal group planarity as critical for potency. All compounds exhibited favorable drug-like properties.

Conclusion: The study successfully identifies P8 and P14 as promising, drug-like lead compounds with a superior BuChE-inhibitory profile, making them viable scaffolds for developing next-generation AD therapeutics. The work validates the combined computational and experimental framework for rational inhibitor design

Simarouba glauca, commonly known as the paradise tree, is a tropical medicinal plant rich in bioactive compounds, including quassinoids, triterpenes, flavonoids, and alkaloids, which exhibit notable anticancer, antimalarial, and anti-inflammatory activities. This mini-review critically examines literature from 2010-present to evaluate the chemical composition, pharmacological potential, and sustainable preparation strategies of these metabolites.

A particular focus is placed on catalyst-free green synthetic approaches, including solvent-minimized extractions, mechanochemical grinding, microwave-assisted isolations, and photochemical or multicomponent transformations. These methods allow the derivatization or isolation of natural products without metal catalysts or harsh reagents, minimizing environmental impact and avoiding residual contamination—key factors in developing clinically viable pharmaceuticals.

In addition, drug-delivery challenges such as poor solubility and limited bioavailability are addressed through literature-reported nano-formulations, liposomal carriers, and polymeric micelles that enhance stability and pharmacokinetic properties. Integrating green synthetic strategies with medicinal-chemistry perspectives highlights the potential of S. glauca metabolites as small-molecule drug candidates and illustrates a pathway toward environmentally responsible pharmaceutical development.

This literature-based perspective demonstrates how combining natural-product chemistry, catalyst-free sustainable methodologies, and modern pharmaceutics can advance drug discovery while reducing chemical waste. The review underscores key research gaps and proposes future directions for translating the bioactivity of Simarouba glauca into safe and sustainable therapeutic applications.

Antimicrobial resistance (AMR) poses a critical global health challenge, necessitating the development of alternative, non-antibiotic strategies. Antimicrobial photodynamic therapy (aPDT) represents a promising approach, employing the combined action of a photosensitizer (PS), visible light, and molecular oxygen to generate reactive oxygen species (ROS) that eradicate microbial cells. In this study, we established a standardized irradiation assay and investigated the suitability of curcumin and five structurally related derivatives as candidate PSs for aPDT applications. The compounds were characterized for their optical absorption properties using UV–Vis spectroscopy and subsequently tested for photodynamic antibacterial efficacy against representative Gram-positive and Gram-negative species: Staphylococcus aureus, Escherichia coli, and Pseudomonas aeruginosa. High-throughput growth inhibition assays were conducted under blue light irradiation (470 nm), enabling determination of half-maximal inhibitory concentrations (IC₅₀).

Curcumin displayed broad-spectrum phototoxicity, achieving bacterial growth inhibition with moderate IC₅₀ values. Several derivatives, including monodemethoxycurcumin and analogues with extended conjugation, exhibited distinct absorption shifts and, in selected cases, enhanced antibacterial potency. However, activity patterns varied across bacterial types, reflecting trade-offs between favorable photophysical properties and effective microbial uptake. These findings underscore the importance of structure–activity relationship (SAR) insights in optimizing PS design.

Overall, curcumin remains a safe and accessible scaffold for aPDT, but targeted chemical modifications—particularly those improving aqueous solubility and penetration of Gram-negative outer membranes—are essential to enhance therapeutic potential. This work provides a framework for rational design of next-generation curcumin-based photosensitizers toward clinically viable antimicrobial photodynamic therapies.

N-Hydroxypeptides have recently attracted attention for their distinct conformational and physicochemical properties, which markedly influence biological activity. However, incorporating N-hydroxyproline into peptide sequences is synthetically demanding, typically requiring complex transformations with several protection/deprotection steps that reduce efficiency and sustainability of the synthesis process. In this study, we present an innovative strategy for the N-hydroxylation of proline in peptides using an on-site oxidation strategy via Cope elimination under mild conditions. The methodology is showcased through the assembly of an N-hydroxylated derivative of melanostatin neuropeptide.

Our approach demonstrates that the N-(cyanoethyl) group serves as a protecting moiety during peptide synthesis and as a leaving group in the oxidation step. Using N-(cyanoethyl)-L-proline as the starting material, peptide coupling with H-L-Leu-Gly-OMe afforded a melanostatin intermediate that, upon treatment with m-chloroperbenzoic acid, underwent an efficient Cope elimination to introduce the N-hydroxy group at the proline residue.

This single-step oxidation under mild conditions delivered the desired tripeptide with excellent yield (93%), avoiding additional deprotection steps. Comparative experiments revealed that incorporating the N-(cyanoethyl) group earlier in the synthesis significantly improved the global yield (78%) relative to late-stage derivatization (41%).

Overall, this work presents a novel strategy for the selective modification of prolyl-containing peptides, exemplified by the assembly of N-hydroxy-melanostatin. This on-site oxidation methodology, based on Cope elimination, offers a valuable tool for the development of bioactive N-hydroxylated peptides.

Intranasal insulin (InI) demonstrates clinical efficacy in mitigating cognitive deficits. Its neuroprotective potential in cerebral ischemia is of growing research interest. For the first time, this study investigates the therapeutic window for InI in a rat model of transient global cerebral ischemia. Cerebral ischemia was induced in male Wistar rats via 10-min bilateral common carotid artery occlusion with hypotension (40 mm Hg) (I/R). Sham-operated (SO) controls underwent surgery without occlusion or hypotension. InI (0.5 IU/rat) was administered at 2 or 4 hours after ischemia, followed by once-daily dosing for 7 days. Hippocampal gene expression and neuronal survival were assessed using RT-PCR and Nissl staining, respectively. InI at 2 h post-ischemia more effectively prevented body weight loss in I/R rats compared to the 4 h regimen. Blood glucose levels remained unchanged across groups. Increased gene expression of GFAP, a marker of astrocytes, and IBA-1, a marker of microglia, was found in the hippocampus of I/R rats, which may indicate astrogliosis and microgliosis. InI, administered at 2 h, normalized the expression of these genes. Moreover, only the 2 h InI treatment group exhibited a significant neuroprotective effect, with a higher density of Nissl-positive neurons in the hippocampal CA1 region compared to untreated I/R rats, consistent with the levels observed in SO animals. This study is the first to define a critical window of opportunity for InI treatment in transient cerebral ischemia. Administration initiated within 2 hours post-ischemia provides neuroprotection and attenuates glial activation, while delayed treatment (4 h) is markedly less effective.

The work is supported by the IEPhB Research Program No. 075-00967-23-00.

Breast cancer remains one of the most significant health risks throughout the world, demanding precise methods for early detection, therapeutic intervention and disease progression monitoring. Despite improving screening and therapy, patient outcomes are highly variable because of complex biology of the disease and therefore validated biological targets and biomarkers are required. Breast cancer heterogeneous disease shaped by genetic, molecular and environmental variables and biomarkers playing a central role in customizing personalized treatment. traditional markers such as hormone receptor (ER, PR) and HER2 status have been applied in clinical decision making but ne research suggests that other molecular signals, circulating tumor cells and microRNAs are promising indicators of tumor behavior and therapeutic response. In this research, tumor tissue and liquid biopsy have been compared using molecular profiling methods and bioinformatics-driven discovery of biomarkers.Immunohistochemistry, PCR-based assays and proteomic techniques have been applied for the identification and validation of novel biomarker panels for specific subtypes of breast cancer. Key findings imply that novel biomarker candidates not only distinguish between aggressive and indolent tumor forms but also predict responsiveness to targeted therapies more accurately over conventional markers. Importantly, integrating these markers in clinical models improved diagnostic specificity and indicated new therapeutic targets for drug development. Identification and validation of new biological targets and biomarkers are the prime innovation of personalized medicine in breast cancer. This research points towards precision oncology's potential to enhance survival and quality of life for patients, offering hope for more effective, individualized treatment regimens in the future.

Introduction: Antimicrobial resistance is a high healthiness problem due to constant limitation of their treatment. Methicillin resistance in Staphylococcus aureus strains is alarming, due to their unresponsiveness to other β-lactams. With the rise of antimicrobial resistance, Photodynamic Inactivation emerges as alternative in concomitant treatment of infections. Photodynamic inactivation technique uses light to activate photosensitizers, which, when irradiated, generate reactive oxygen species, leading to cell death and cytoskeletal disruption.

Methodology: Zincoporphyrin, ZnP, (ZnTE-2-PyP⁴⁺) was used as a photosensitizer (final concentration 4 μmol∙L^-1), and oxacillin at concentrations of 8 mg∙L^-1, 4 mg∙L^-1, 2 mg∙L^-1, 1 mg∙L^-1, and 0.5 mg∙L^-1 in Mueller-Hinton Broth. Strain of Staphylococcus aureus MRSA was grown on Mueller-Hinton Agar at 35 ± 1 °C for 24 h, with preparation of suspensions in Saline solution (0.9% w/w) adjusted to optical density (OD) of 0.1 at 625 nm, corresponding to 1.0∙10⁸ cells∙mL^-1 with final working solution of 106 cells∙mL^-1. Equals aliquots of ZnP and previous solution were mixed and irradiated for 3 min (6.26 J∙cm^-2) under blue light, with subsequent exposure of MRSA+ZnP to oxacillin concentrations and incubated at same conditions, with subsequent visual reading to determine the Minimum Inhibitory Concentration. Control conditions in absence of light were performed to ensure the reliability of the tests.

Results and discussion: The light-treated systems showed a reduction in minimum inhibitory concentration on oxacillin from 8 mg∙L^-1 to 0.5 mg∙L^-1. The systems not exposed to light continued to show oxacillin resistance. The momentary susceptibility to oxacillin in the light-treated group may be due to damage to the bacterial cell wall caused by the photodynamic treatment.

Conclusion: It was observed that concomitant treatment of IFD and oxacillin presents a positive in vitro perspective for infections caused by Staphylococcus MRSA, playing an important role in antimicrobial resistance.

Ziprasidone Hydrochloride is an atypical antipsychotic drug commonly prescribed for the treatment of schizophrenia. Its clinical efficacy is significantly limited by its very low aqueous solubility (<0.1 mg/mL), which restricts oral absorption and systemic bioavailability. In the present study, we aimed to enhance the solubility and dissolution rate of Ziprasidone Hydrochloride through the formulation of solid dispersions using hydrophilic polymers, including polyethylene glycol 6000 (PEG6000), polyvinylpyrrolidone (PVP), hydroxypropyl methylcellulose (HPMC), and hydroxypropyl cellulose (HPC). Solid dispersions were prepared by the solvent evaporation technique in various drug-to-polymer ratios and subjected to comprehensive physicochemical characterization. The formulations were analyzed using Scanning Electron Microscopy (SEM), Fourier Transform Infrared Spectroscopy (FTIR), Differential Scanning Calorimetry (DSC), and X-Ray Diffraction (XRD) studies. The results revealed that incorporation of Ziprasidone into polymer matrices led to a reduction in particle aggregation, conversion from crystalline to amorphous form, and improved wettability and dispersibility. Optimized solid dispersions exhibited approximately a 50% increase in solubility compared to the pure drug. Dissolution studies demonstrated a significant improvement in release profiles, with drug release directly proportional to the polymer concentration. Among the polymers tested, PVP was the most effective in enhancing solubility and dissolution. These findings indicate that polymer-based solid dispersions are a promising strategy for improving the oral bioavailability and therapeutic efficacy of poorly water-soluble drugs like Ziprasidone Hydrochloride.