Drug Chemistry

BIOMEDICAL JOURNAL OF PIROGOV UNIVERSITY (MOSCOW, RUSSIA)

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Stolbov LA, Tarasova OA, Borisevich SS, Gorokhov YV, Zarubaev VV, Poroykov VV

We created classification models to study how the structure of A/H1N1 flu inhibitors relates to their activity (structure-activity relationship (SAR) models). These models rely on a unique machine learning approach known as a self-consistent extreme classifier. The training sample consisted of expert-selected information regarding the structures and biological test outcomes of 2,255 drug-like compounds. Independent variables included the IC50 (50 % inhibitory concentration), the CC50 (half-maximal cytotoxic concentration), and the SI (selectivity index). The structure was described using molecular descriptors called quantitative atomic neighborhoods (QNA). The predictive accuracy (AUC-ROC) for the IC50, CC50, and SI values was 0.822, 0.875, and 0.875, respectively. Evaluation of the developed models on an independent test set of 16 diverse chemical compounds demonstrated a classification accuracy of 63 % for predicting antiviral activity and cytotoxicity. The study shows that original SAR models can be used to select promising drugs to fight the A/H1N1 flu virus before they are made or tested in a lab.

Received: 2026-01-29

Published online: 2026-06-15

DOI: 10.24075/dc.2026.008

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VIEWS 13

Kopylova TA, Sokolova AS, Yarovaya OI, Salakhutdinov NF

Despite the clinical success of five boronic acid-based organoboron compounds, the literature highlights a critical gap in our understanding of amine-borane adducts, a highly promising class of boron compounds. The objective of this paper is to classify data regarding the mechanisms of action of existing boron-based pharmaceuticals, while assessing the structural, stability, and biological properties of amine-borane adducts as future therapeutic candidates. This analytical review examines organoborane pharmacophores, specifically analyzing the donor-acceptor properties of the B-N bond and how electronic and steric factors influence them. It also summarizes the in vitro and in vivo pharmacological test results for various amine-boranes, including adducts of alpha amino acids, nucleosides, and heterocyclic amines. The study’s core methodologies included evaluating structural activity relationships and testing antitumor, anti-inflammatory, lipid-lowering, and pain-relieving effects in standard preclinical models (e. g., Ehrlich ascites, L1210, P388, HLB, SW480, and edema/pleurisy models). Additionally, cytotoxicity was measured using ED50 values across various tumor cell lines. In summary, amine-borane complexes are a highly promising class of compounds with proven antitumor, anti-inflammatory, and lipid-lowering properties, which are strongly dictated by their structures. Nevertheless, their successful translation into clinical drugs relies on closely examining the stability of the B-N coordination bond and their reactivity under physiological conditions, including hydrolysis, oxidative stress, and interactions with biological nucleophiles in vivo.

Received: 2025-12-29

Published online: 2026-05-30

DOI: 10.24075/dc.2026.006

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VIEWS 28

Zarubaev VV, Lavrentieva IN

Measles is a severe highly contagious and vaccine-preventable disease. Before the introduction of the measle vaccine in the 1960s, an estimated 30 million cases and over 2 million deaths were recorded annually [1]. In industrialized nations, measles mortality declined during the early 20th century due to economic development, better nutrition, and enhanced supportive care, particularly antibiotic therapy for secondary bacterial pneumonia [2]. Measles mortality rates (MR) range from less than 0.01% to over 5%, largely driven by average age of infection, nutritional status, vaccination coverage, and access to medical care [3]. Measles is the leading cause of mortality among displaced populations (especially in refugee camps), whereas MR among children from major humanitarian crises was estimated at 20–30% [4]. Measles is less severe in vaccinated individuals with weak immune systems, and mortality rates in this group are lower than for measles cases in unvaccinated individuals. Increased vaccination coverage often shifts the burden of disease from average ages toward older adults with severe clinical courses and high MR.

Received: 2026-01-19

Published online: 2026-03-23

DOI: 10.24075/dc.2026.005

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VIEWS 143

Popov NS, Gavrilenko DA, Baranov MS, Kaurova DE, Myasnyanko IN, Balabanyan VYu, Ivanov DS

Sydnonimines represent a promising class of chemical compounds for the development of new drugs, exhibiting a wide spectrum of pharmacological activity. Due to their ability to release nitric oxide and exert a vasodilatory effect, these compounds are potential candidates for the development of drugs for correcting cerebral circulation disorders. The present study is aimed at optimizing lead compounds of the sydnonimine group to create a drug candidate possessing predominant cerebral vasodilatory activity. The objects of the study were N-(ethoxycarbonyl)sydnonimine derivatives containing various substituents at the 3-position of the 1,2,3-oxadiazole ring. In a pharmacological experiment on rats, using a validated chromatographic-mass spectrometric method, the concentration of lead compounds in blood plasma and brain tissues was assessed after a single intragastric administration, and tissue distribution coefficients were calculated. The mean brain/plasma tissue distribution coefficients significantly differ among the studied substances. Compounds with radicals in their structure such as decyl, octyl, and 4-methylhexan-2-yl (BBP2023) predominate in CNS tissues compared to blood plasma throughout the entire observation period. Among the studied substances, the lead compound BBP2023 is of greatest interest, for which cerebral vasodilatory activity, an optimal pharmacokinetic profile, and pleiotropic effects (procognitive, psychostimulant) have been established. This drug candidate is recommended for further expanded preclinical studies.

Received: 2026-02-16

Published online: 2026-03-13

DOI: 10.24075/dc.2026.003

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VIEWS 376

Melchenko MA, Yarovaya OI

Protecting against ionizing radiation is a critical challenge in medicine and radiobiology due to the increasing use of radiotherapy in oncology and the risk of radiation accidents. The development of effective and safe radioprotective agents remains associated with significant problems and limitations. The paper explores recent data on radioprotectors (preventive agents) and radiomitigators (agents that mitigate the effects of radiation), as well as current problems of their development and application. Classical synthetic aminothiols (amifostine) as well as modern strategies, including proinflammatory cytokine inhibitors (TGF-β), statins, ACE inhibitors, probiotics, and natural antioxidants, were analyzed. Fundamental limitations hindering widespread clinical use including a narrow therapeutic window, toxicity, and lack of selectivity toward healthy tissues during radiation therapy, have been identified. Although an ideal radioprotective drug has not been developed yet, modern research has advanced, shifting focus toward comprehensive radiation mitigation strategies to address delayed effects of radiation exposure.

Received: 2025-11-19

Published online: 2026-03-12

DOI: 10.24075/dc.2026.004

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VIEWS 246

Ubushaev SV, Sepp VV, Bakulin KS, Sen OYu

Validation of analytical methods for poorly soluble BCS Class II/IV drugs like Aprepitant in aqueous media is complicated due to instability of samples at the stage of preparation. The goal of the research is to detect the mechanism of loss of Aprepitant analytical signal during filtration and determine the conditions for an exact diagnosis. In this paper, the effect of membrane materials (PES, PVDF, Nylon, PP) on analyte concentration measurements via UV spectrophotometry was examined. Filtration of aqueous solutions is established to cause significant analyte losses ranging from 15.1% (PP) to 83.9% (PES), depending on the initial concentration. It is proved that the main loss factor is not passive adsorption, but mechanically induced heterogeneous nucleation on the membrane surface, which is confirmed by an increase in optical scattering within the 300–500 nm range. Fraction filtration revealed abnormal desorption effects on PES filters. It has been shown that the use of an acidic medium (0.1 M HCl) prevents nucleation due to protonation of the molecule: filtration losses are reduced to statistically insignificant values (<1.6%). To ensure the accuracy of aprepitant analysis, it is recommended to exclude filtration of neutral aqueous solutions, replacing it with centrifugation, or to use acidic dissolution media.

Received: 2026-01-21

Published online: 2026-02-25

DOI: 10.24075/dc.2026.002

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VIEWS 175

Kiseleva NM, Korolev AG, Inozemtsev AN, Romanov BK

The abstract presents the results of research that reported how immune and nervous systems collaborate to regulate learning and memory processes. The research was conducted by the Department of Higher Nervous Activity of Lomonosov Moscow State University from 2009 to 2020. Wistar rats served as experimental subjects. A study was made of the effect of thymic preparations such as tactivin, 5th fraction of thymosin and thymalin on production of conditioned reflexes (conditioned active avoidance reflex (СAAR), conditioned passive avoidance reflex (СPAR), conditioned food-procuring reflex (CFPR) both in normal and pathological conditions (thymectomy, aging, neurotoxic effect of heavy metals and 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)). Research indicates that thymus peptides showed a positive effect on cognitive functions. In normal conditions, they enhanced production of CAAR and CFPR with a prolonged retention of the memory trace in the CPAR task. Thymectomy resulted in restoration of conditioned reflexes lost after surgery. Cognitive functions were also improved in 18–24-month-old rats and following neurotoxic exposure. Thus, thymus peptides exert broad regulatory effects beyond immunity. The thymus also communicates with the central nervous system (CNS), potentially influencing cognitive processes like learning and memory.

Received: 2026-01-19

Published online: 2026-02-16

DOI: 10.24075/dc.2026.001

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VIEWS 142