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Using the methodology of “click” chemistry, a singular method has been developed for the synthesis of unique conjugates based on sesquiterpene lactones: dehydrocostuslactone and alantolactone with polyalkoxybenzenes. To expand the structural range of the resulting conjugates, the length of the 1,2,3-triazole spacer was varied. For all synthesized compounds, the cytotoxic profile was determined on the cell lines of tumor origin (SH-SY5Y, HeLa, Hep-2, A549) and normal Hek 293 cells. It was found that the compounds based on alantolactone 7a–d with a long spacer and substances containing dehydrocostuslactone 10a–d with a short spacer have the greatest toxic effect. The decrease in cell survival under the action of these conjugates may be due to their ability to cause dissipation of the transmembrane potential of mitochondria and inhibit the process of glycolysis, leading to cell death. The obtained results confirm the assumption that the development of conjugates based on sesquiterpene lactones and polyalkoxybenzenes can be considered as a promising strategy for the search for potential antitumor agents.

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Neutrophil dysfunction plays a considerable role.in systemic lupus erythematosus (SLE) The protective function of neutrophils is carried out through various mechanisms: isolation of granular antimicrobial peptides (gAMP), microbial phagocytosis with subsequent degradation via reactive oxygen species inside the phagolysosomes; as well as bactericidal action due to the release of networks from chromatin and gAMP, also called neutrophil extracellular traps (NECTs). The development of neutropenia in SLE has multiple causes, including the formation of antibodies directly to leukocytes; that of neutralizing autoantibodies to the growth factors of neutrophils and cells - myeloid precursors; bone marrow suppression; involvement of neutrophils in the processes of apoptosis and NETosis. Neutrophils in SLE are characterized by reduced phagocytic ability and pathological oxidative activity. In SLE, there is a decrease in the ability to remove the products of neutrophil apoptosis, which is correlated with disease activity. SLE patients are noted to have a higher expression level of the genes specific for low-density granulocytes, an abnormal immature neutrophil population. The impaired processes of formation of NECTs and removal NETosis products play a substantial role in the pathogenesis of SLE. It is shown that the abnormal formation of NECTs also causes endothelial injury and increases the risk of thromboses. The design of novel drugs that act on the specific parts of the formation of NECTs or contribute to their removal from the extracellular environment can propel therapy for SLE and other autoimmune diseases to new heights. There is evidence for further investigations of neutrophil-mediated pathogenetic processes in SLE in order to identify potential therapeutic targets and to understand the mechanisms of action of drugs used in clinical practice.

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Aim.To evaluate the effectiveness of different regimens of maintenance chemotherapy after the first line of treatment for patients with metastatic colorectal cancer.Materials and methods.We performed retrospective analyses of the data from 432 patients from 17 clinics in 14 regions of the Russian Federation who started systemic therapy for metastatic cancer in 2013. The main inclusion criterion was objective response or stabilization after the first 16 weeks of first-line therapy. Four groups of patients were compared, depending on the nature of maintenance therapy: those receiving fluoropyrimidines, a combination of fluoropyrimidines with bevacizumab, monotherapy of bevacizumab and monotherapy of anti-EGFR antibodies. The main criteria for assesment of the effectiveness of treatment were progression-free survival and overall survival. The statistical analysis was performed with the SPSS 20.0 sof tware package.Results.Maintenance therapy after completion of the first 16 weeks of the 1st line of chemotherapy was administered in 126 patients, most of them were treated with fluoropyrimidines (53.1 %). The median overall survival in the maintenance group was 27 versus 21 months in the observation group, p=0.01, HR=0.78 (95 % CI 0.6–1.02) Median progression-free survival in the maintenance group was 11 vs 7 months in the observation group (p<0.001, HR=0.6, 95 % CI 0.5–0.8). The worst results of progression-free survival were observed in the group with monotherapy of bevacizumab – median was 10 months versus 12 months in the fluoropyrimidine monotherapy group, 10 months for the combination of fluoropyrimidine with bevacizumab and 14 months for monotherapy of the anti-EGFR (p=0,9, HR=1.0, 95 % CI 0.9–1.2).Conclusions.There were no statistical differences in survival with different regimens of maintenance therapy. Monotherapy of bevacizumab in maintenance treatment was associated with the worst sur vival rates.