RESUMO
BACKGROUND: At present, more than 8000 sesquiterpene lactones have been isolated and described from natural sources, a significant part of which has cytotoxicity and antitumor activity. One of the practically available sesquiterpene lactones is arglabin, which, as a renewable material, is used for the synthesis of new compounds. The article presents data on the study of cytotoxicity and antitumor activity of the arglabin and its derivatives using molecular modeling methods and, in the experiment in vitro and in vivo. AIM: The aim of this work is to study the cytotoxicity and antitumor activity of new compounds based on the sesquiterpene lactone arglabin using molecular modeling and experimental pharmacology. METHODS: ChemDraw programs and a set of AutoDock programs were used for computer simulation. Molecular docking was carried out using the Maestro graphical interface of the Schrödinger Suite software package (Schrödinger, LLC, New York, NY, 2017). Docking modes standard precision and XP (extra precision) were used. In in vitro experiments, the antitumor activity of compound samples was studied in models of 60 human tumor cell lines, and clonogenic C6 rat glioma cells. The antitumor activity of the samples was studied in experiments in vivo on white outbred rats with transplanted tumors and was evaluated by the inhibition of tumor growth and the magnitude of the increase in average life expectancy. CONCLUSION: When studying the antitumor activity on 60 cell lines of tumor cells (NCI60), clonogenic cells of C6 rat glioma, a high antitumor activity of some arglabin derivatives was established. The connection between the structure of arglabin derivatives and their inhibitory effect on farnesyl protein transferase, topoisomerases -I and -II was studied.
RESUMO
The use of medicinal plants has increased significantly in recent years. More than 80% of the world's population uses medicinal plants to treat themselves. Many antibacterial and anti-inflammatory synthetic drugs are available in medical practice. However, recent tendency of increasing capability of resistance of bacteria to usage of antibacterial drugs of different groups is taking place. Considering the wide range of pharmacological and antimicrobial activity of safflower flower extracts and available vitamins in their composition, it was decided to create a preparation based on the CO2 extract of safflower (Carthamus tinctorius L.) in the form of an ophthalmic emulsion. The aim of this research is to study the composition and antimicrobial activity of the extract and ophthalmic emulsion drops against test strains of microorganisms. The subject of this study is the ophthalmic emulsions from flowers of Kazakhstan species of "Akmai" safflower, collected in the flowering stage in southern Kazakhstan in August 2021. The component composition was determined using gas chromatography with the Agilent 7890A/5975C mass spectrometry technique. A study of the antimicrobial activity of the ophthalmic emulsion drop extracts was performed with two strains of Gram-positive bacteria, one strain of Gram-negative bacteria, and one culture of fungi. The following biologically active substances were determined from the GC-MS results: tridecane 94%, tricosane 93%, hexacosane 93%, dodecanoic acid 92%, pentacosane 91%, and linoleic acid 63.7%. The investigated emulsion-type eye drop shows bactericidal activity against S. aureus ATCC 6538-P, where the zone of growth suppression under the ophthalmic emulsion action corresponded to 9.0 ± 0.0 mm. The tested ophthalmic emulsion drops show the presumed biological activity against conditionally pathogenic bacteria. The results of chromatographic analysis and antimicrobial activity of the tested samples indicate the prospects for their further study for use as anti-infectious (anti-inflammatory) agents in medicine.
