Study of the cytostatic effect of a new compound of the tropolon series on primary cultures of glioma cells.

Abstract

e14056 Background: Brain tumors present a genuine challenge for medicine due to their anatomical features, high resistance to existing chemotherapeutic drugs, a strongly immunosuppressive environment, and the presence of the blood-brain barrier. The research and development of new anti-tumor drugs remains an important task. Tropolone derivatives represent a promising class of organic compounds that could serve as new pharmaceutical anti-tumor agents. There is currently a growing interest in tropolone alkaloids, as many of them possess a broad spectrum of pharmacological activity. The aim of the study was to investigate the cytotoxic effect of a new tropolone derivative 2-(1,1-dimethyl-1H-benzo[e]indoline-2-yl)-5,6,7-trichloro-1,3-tropolone (JO-122(2)) on primary glioma cell cultures in an in vitro experiment. Methods: The tumor material for primary cell cultures was obtained from a patient who was diagnosed with grade 4 glioblastoma on the background of anaplastic astrocytoma (Culture 1) and a patient with histologically verified grade 4 giant cell glioblastoma (Culture 2) who were treated at the Department of Neuro-Oncology of the National Medical Research Centre for Oncology of the Ministry of Health of the Russian Federation. Cell cultures were cultured on DMEM medium (Gibco, USA) with the addition of 10% FBS (Hyclone, USA). The cells were planted in a 96-well plate (Eppendorf, Germany) in the amount of 5,000 cells in 100 µl of medium per well and incubated for 24 hours at a temperature of 37 ° C in an atmosphere containing 5.0% CO2. After 24 hours, the culture medium was replaced with a medium containing JO-122(2) in a series of double dilutions. The maximum amount of JO-122(2) was 24 μmol. The MTT test was performed according to the standard procedure, the exposure time was 24, 48 and 72 hours. The optical density was determined at a wavelength of 540 nm using a tablet reader. The inhibition index (IC50) was defined as the percentage of surviving cells after exposure to JO-122(2) from the control. Results: The results of the in vitro cytotoxic effect study showed that the IC50 for Culture 1 after incubation with the addition of JO-122(2) for 24 hours was 5.3668 μmol, 48 hours - 3.9358 μmol, 72 hours - 1.5418 μmol. For Culture 2, the IC50 after incubation for 24 hours was 2.9146 μmol, 48 hours - 2.1581 μmol, 72 hours - 1.1187 μmol. Conclusions: Our results indicate that JO-122(2) has a pronounced cytotoxic effect on primary glioma cell cultures. It is noted that an increase in the duration of incubation contributes to a decrease in cell viability.