New derivatives of phaeosphaeride A (PPA) were synthesized and characterized. Anti-tumor activity studies were carried out on the HCT-116, PC3, MCF-7, A549, К562, NCI-Н929, Jurkat, THP-1, RPMI8228 tumor cell lines, and on the HEF cell line. All of the compounds synthesized were found to have better efficacy than PPA towards the tumor cell lines mentioned. Compound 6 was potent against six cancer cell lines, HCT-116, PC-3, K562, NCI-H929, Jurkat, and RPMI8226, showing a 47, 13.5, 16, 4, 1.5, and 7-fold increase in anticancer activity comparative to those of etoposide, respectively. Compound 1 possessed selectivity toward the NCI-H929 cell line (IC₅₀ = 1.35 ± 0.69 μM), while product 7 was selective against three cancer cell lines, HCT-116, MCF-7, and NCI-H929, each having IC₅₀ values of 1.65 μM, 1.80 μM and 2.00 μM, respectively.

Development of drug delivery systems is one of the high-priority areas in pharmaceutical technologies. Currently, most of the largest pharmaceutical companies are developing delivery systems, both for new drugs and for already existing ones. Oncology has been and still remains one of the leading application areas for these systems. A variety of problems to be solved in the development of delivery systems has led to the emergence of numerous options for such systems. Each of these options has its pros and cons. The specificity of drug delivery systems and their diversity has led to the necessity of information systematization about their physical and technological characteristics and applicability in clinical practice. This review generalizes and systematizes information about modern targeted delivery systems for medicinal compounds with low bioavailability that is described in the scientific literature and is used in modern pharmaceutical technology. Particular importance is given to the trends of nanoscale delivery systems development for various therapeutic drugs that can penetrate protective barriers of body, achieve sustained controlled release, and are also promising for delivery to target cells. Nanoscale drug delivery systems have higher potential for pharmaceutical and medical industries. The following nanoscale systems for drug delivery were identified: nanoemulsions, nanocapsules, nanoliposomes (including exosomes, virosomes, and other modifications of traditional liposomes), dendrimers, and carriers based on cells and peptides. Their main technological and pharmacological characteristics were given, and the prospects for their clinical use were considered. The base methods of each drug delivery systems formation were also described. It has been shown that the interest in modifications of liposomal systems (exasoms) as well as in dendrimers and cell-based delivery systems increases every year.

Uric acid (UA) is the end product of purine metabolism and a substance that promotes a chronic inflammatory process. One of the mechanisms of inflammation associated with the UA is the ability of its crystals, mainly monosodium urate, to activate NLRP3 inflammasomes, classifying UA and its salt crystals as damage-related molecular patterns (DAMPs). These crystals also activate the complement system, leading to increase in C3a, C4a, and C5a concentrations and excessive consumption of complement system proteins. It has been known for a long time that UA is able to activate complement, but the relationship between hyperuricemia and complement system functional activity, which can be assessed by complement-mediated hemolysis, remains unclear. In this study, we have made an attempt to estimate the UA concentration that does not lead to spontaneous complement system activation. The study assessed the relationships between the parameters of complement functional activity and some blood biochemical data with UA concentration ([UA]) using correlation analysis. The rate (Vlys) and time of 50% hemolysis (T50) were considered as indicators of complement functional activity, and their relationship was demonstrated using exponential functions y = a*e[x], which takes the form y = [UA]*e[C3]. Concentration of C3 is the argument of the function, base of degree is the base of the natural logarithm, and the proportionality coefficient equal to the UA concentration. Correlation analysis showed the inverse dependent between function values and the corresponding values of T50 (r = -0.83, p 0.0001) in the range of UA concentration exceeding 370 umol/L, which is near to the upper limit of the normal level for women and is within the normal range for men. Thus, the approach to assess the effect of UA on complement activation using the analysis of the complement hemolytic activity is effective to demonstrate the pathogenetic function of UA in the development of the inflammatory process without involving inflammasomes through the direct effects on complement activation processes. The relationships demonstrated suggest that the upper limits of the range of “normal” UA concentrations are arbitrary, and their revision is likely advisable.

The utility of animal models in preclinical research depends on the completeness of our knowledge about these models. Nonhuman primates are the closest animal model to humans, available for preclinical evaluation of biotechnological products. The lack of immunogenetic characteristics of the primates used in a particular study significantly limits the possibilities of analyzing the results obtained. The availability of information about the haplotype of the major histocompatibility complex (MHC) increases the overall significance of the model. Genotyping of primates at the MHC locus by DNA analysis is excluded, since the representation of individual MHC proteins depends on the level of their expression in immune cells, rather than on their presence in the genome. Therefore, the genotyping of primates at the MHC locus is carried out by analyzing mRNA encoding allelic variants of proteins. This work presents the results of genotyping of a sample of rhesus macaques from the collection of the Kurchatov Complex of Medical Primatology by a next-generation sequencing technology using an IonProton sequencer.