INDICATORS OF CELL METABOLISM IN VITRO IN RESEARCHES OF ANTI-INFLAMMATORY AND CYTOTOXIC EFFECTS OF FULLEROPYRROLIDINES С60 AND THEIR INITIAL SUBSTRATES
Authors:   corresponding member of NAS RK, Doctor of chemical sciences, Professor, Institute of Organic Synthesis and Coal Chemistry of the Republic of Kazakhstan, Karaganda, Kazakhstan, Fazylov S. D. ,   iosu8990@mail.ru,   https://orcid.org/0000-0002-4240-6450, Nurkenov O. A. ,   Doctor of chemical sciences, Professor, Institute of Organic Synthesis and Coal Chemistry of the Republic of Kazakhstan, Karaganda, Kazakhstan; nurkenov_oral@mail.ru; https://orcid.org/0000-0003-1878- 2787, Arinova A. E. ,   a, Doctoral student of Buketov Karaganda State University, Karaganda, Kazakhstan; arinova-anar@mail.ru; https://orcid.org/0000-0002-7780-4555, Gazaliev A. M. ,   Academician of the National Academy of Sciences of the Republic of Kazakhstan, Deputy Director for Research, Institute of Organic Synthesis and Coal Chemistry of the Republic of Kazakhstan, Karaganda, Kazakhstan; https://orcid.org/0000-0003-2161-0329, Bakirova R. E. ,   Doctor of medical sciences, Professor, «Karaganda Medical University» non-commercial joint-stock company, Karaganda, Kazakhstan; bakir15@mail.ru; https://orcid.org/0000-0002-1592- 8579, Ibraev M. K. ,   Doctor of chemical sciences, Professor, Karaganda State Technical University, Karaganda, Kazakhstan; mkibr@mail.ru; https://orcid.org/0000-0003-0798-5562, Takibayeva A. Т. ,   head of the Department "Chemistry and chemical technology", Karaganda State Technical University, Karaganda, Kazakhstan; altynarai81r@mail.ru; https://orcid.org/0000-0003- 0536-0817, Fazylov A. S. ,   undergraduate of the Karaganda State Technical University, Karaganda, Kazakhstan; arman1708@yahoo.com; https://orcid.org /0000-0003-2905-9121
Published: October 2020

The article considers data on the in vitro study of new fulleropyrrolidine compounds for anti-inflammatory and cytotoxic activity in cultures of human monocyte cell lines MonoMac-6 and THP-1Blue and also as inhibitors of human neutrophil elastase. This enzyme is a regulator of inflammation. In different situations, it can act both as a pro-inflammatory and as an anti-inflammatory agent. An imbalance in the regulation of elastase activity plays an important role in the pathogenesis of cystic fibrosis, acute respiratory distress syndrome, bronchiectasis, chronic obstructive pulmonary disease, type 2 diabetes mellitus, atherosclerosis and hypertension. In the future, such studies should lead to the creation of optimal in vitro models that most adequately reflect the situation in vivo and establish the relationship between the structure and activity of the studied drugs. It is noted that the presence of lipophilic properties in fullerene C60 derivatives is especially important in the development of pharmaceuticals for the control of pathogens of various infectious diseases. Fullerene C60 derivatives have the ability to easily penetrate lipid membranes, overcome the blood-brain barrier, and modulate ion transport. Compounds were tested for anti-inflammatory and cytotoxic activity (in vitro) on cultures of human monocytic cell lines MonoMac-6 and THP-1Blue. Modified fullerene compounds of various structures were tested for their inhibitory ability against neutrophil elastase enzyme (in vitro). Elastase activity was evaluated by the ability of fulleropyrrolidine compounds to hydrolyze the synthetic substrate N-methylsuccinyl-Ala-Ala-Pro-Val-7-amino-4-me-thylcoumarin (Calbiochem). The results of studies of fullerene compounds in relation to their anti-inflammatory and cytotoxic activity are obtained. The analysis of the fluorescence kinetics of the compounds was carried out. The cytotoxic activity of the samples was investigated in the Brine Schrimp test using Artemia salina. All compounds have cytotoxicity, which suggests a lack of selectivity of chemotherapeutic action. In general, the presence of a cytotoxic effect confirms the reality of antimicrobial action. The results of the study of the antibacterial and antifungal activity of the synthesized new fulleropyrrolidines and their starting substrates are described (S. aureus 505, Bacillus subtilis, Str.agalactiae, E. Coli M-17, Ps.aeruginosa, Candida аlbicans, Penicillium citrinum, Aspergillus niger, Aspergillus flavus, Trichophyton mentagraphytos, Epidermophyton fioccosum). As a result of the study of the potential antifungal activity of the compounds, it was found that only two drugs inhibit the growth of test cultures in vitro. All other studied samples have practically no activity against the yeast fungi Candida albicans. In general, the presence of a cytotoxic effect in the studied fullerene compounds confirms the reality of the antimicrobial action.