Drug Chemistry

BIOMEDICAL JOURNAL OF PIROGOV UNIVERSITY (MOSCOW, RUSSIA)

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Rudakova MA, Negrebetsky VV

The review evaluates contemporary strategies in developing multi-target drugs for neurodegenerative diseases based on sulfonic acid derivatives and heterocyclic compounds. Special emphasis is placed on taurine and homotaurine as promising pharmacophores with a broad spectrum of biological activities, including antioxidant, anti-inflammatory, anti-apoptotic, and neuromodulatory effects. Data from both experimental and clinical trials are evaluated, indicating that these agents effectively target critical pathways in the pathogenesis of Alzheimer’s disease, Parkinson’s disease, ischemic brain damage, and other disorders of the central nervous system. The underlying molecular mechanisms of their action are reviewed, including the regulation of GABAergic transmission, attenuation of neuroinflammation, inhibition of beta-amyloid aggregation, and preservation of neuronal survival under oxidative stress. Information on the neuropharmacological potential of pyridine, pyrimidine, and uracil derivatives is also presented, highlighting their capacity to act as multi-target agents through interactions with diverse molecular targets. The prospects of creating hybrid molecules that combine the properties of aminosulfonic acids and heterocyclic fragments to enhance the efficacy, selectivity, and pharmacokinetic profiles of neuroprotective agents are discussed. The conclusion is made about the high prospects of this field for development of novel therapeutic agents capable of simultaneously targeting multiple pathogenetic mechanisms of neurodegenerative diseases.

Received: 2026-06-12

Published online: 2026-06-30

DOI: DOI: 10.24075/dc.2026.013

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VIEWS 96

Kalinin EV, Chechina PA, Yermolaeva SA

Growth factors (GFs) are molecules that regulate cellular proliferation, differentiation, migration and survival. The review delves into nine basic families of the molecules and how they are utilized in medicine. The most substantial clinical evidence supporting medical applications has been established for EGF (epidermal growth factor), PDGF (platelet-derived growth factor), and FGF (fibroblast growth factor), which are primarily indicated for the treatment of chronic, non-healing wounds, particularly in patients with diabetes mellitus. Data from recent systematic overviews indicate that EGF yields the highest efficacy in terms of healing rate and complete wound closure. In Russia, an EGF-based pharmaceutical agent (Heberprot-P®) has obtained regulatory approval. It is officially included in national medical recommendations. Globally, approved pharmaceutical analogs incorporating PDGF, FGF, NGF, and proteins are employed to promote bone tissue regeneration. Furthermore, key limitations are addressed: precise delivery of these molecules to target tissues, safety of chronic utilization, and a critical need for further extensive investigations. Novel approaches are explored, such as the screening for substances capable of substituting natural growth factors, as well as combined therapies. The role of these signaling systems in tumorigenesis and development of anti-cancer drugs is also discussed.

Received: 2026-05-29

Published online: 2026-06-21

DOI: 10.24075/dc.2026.012

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VIEWS 120

Gusev RA, Kramarova EP, Volchenkov TI, Korlyukov AA, Lagunin AA, Baukov YuI, Shmigol TA, Negrebetsky VV

A comprehensive study of 10 N-sulfopropylated uracil derivatives (7–16), differing in substituents at positions C(5) and C(6) (H, CH3, NO2, Br, Cl, I, NH2), including 36 possible tautomeric forms, was carried out using methods of quantum chemistry (ωB97X-3c, CPCM) and prediction of the spectrum of biological activity in silico (PASS and PharmaExpert programs, version 2024). In every case, diketo-tautomer a is the dominant form in the condensed phase (ΔΔG=0). Depending on the substituent, the relative Gibbs energy values for keto-enol tautomers b and c range from 36 to 122 kJ/mol. It has been shown that the introduction of a sulfopropyl group does not violate the tautomeric preferences of unsubstituted uracil. A wide range of biological activity of the investigated structures was predicted using QSAR analysis. Antiviral effects (including HIV activity), antibacterial effects, anti-ischemic activity, and neuroprotective effects associated with inhibition of beta-amyloid aggregation were the most highly anticipated outcomes. The potential risks of hemotoxicity and peripheral neuropathy for nitro derivatives have been revealed (9). Diketo forms of N-sulfopropylated uracils with moderate electron-donor substituents are promising candidates for the development of multitargeted neuroprotective and antiviral drugs.

Received: 2026-05-29

Published online: 2026-06-16

DOI: 10.24075/dc.2026.011

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VIEWS 135

Sepp VV, Rusakov VM

This mini-review of scientific literature highlights novel approaches that assess bioavailability and bioequivalence of drugs using the In Vitro Permeation Test (IVPT). The test is widely applied to explore transdermal and skin permeation of drugs. IVPT is an essential tool of preclinical and regulatory quantitative assessment of the rate and extent of active substance permeation via the skin under controlled lab conditions. The interest in this approach has risen significantly in recent years, as it was necessary to develop more sensitive, reproducible and ethically acceptable methods assessing drugs for topical administration. Emphasis is given on analyzing the possibilities of IVPT to confirm bioequivalence of original and reproduced drugs and comparing the method with traditional clinical and pharmacokinetic approaches. Moreover, the existing limitations of IVPT associated with variability of biological models and complex extrapolation of the obtained data to clinical conditions are discussed. The prospects for standardization, optimization and subsequent adaptation of this method and its role in novel programs assessing quality, effectiveness and therapeutic equivalence of topical drugs have been explored.

Received: 2026-04-19

Published online: 2026-06-13

DOI: 10.24075/dc.2026.010

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VIEWS 149

Ovsyannikova MA

Biological contamination within cell lines poses a critical challenge, resulting in substantial expenses across both research laboratories and industrial manufacturing. The introduction of contaminants into cell lines compromises the validity of the data and requires subsequent replication of the assays. There exists a remarkably extensive array of contaminants involved, ranging from readily identifiable fungi to hidden mycoplasmas and specific viruses like the murine hepatitis virus and BVDV. As decontamination of infected cultures poses significant risks, the immediate rejection of affected materials stands as the most viable protocol. Biosafety within large enterprises can be optimized through the deployment of an integrated database and PCR-based diagnostic algorithm. By evaluating the sensitivity, specificity, duration, and cost of each technique, it can be concluded that PCR is the optimal strategy for massive structures. A centralized database synchronizes laboratory data streams, eliminating the latent risks of pathogen transmission via common equipment. The systematic registration of incidents and exchange of data on selected primers make it possible to quickly eliminate recurrent problems and achieve substantial cost optimization.

Received: 2026-04-21

Published online: 2026-06-06

DOI: 10.24075/dc.2026.009

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VIEWS 127

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 175

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 174

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 278