Evaluation of the cytotoxic activity and toxicity of a tropolone derivative with a potential antitumor effect
The aim. To study the toxicity of 2-(6,8-dimethyl-5-nitro-4-chloroquinoline-2-yl)-5,6,7-trichloro-1,3-tropolone in vitro and in vivo.Materials and methods. 2-(6,8-dimethyl-5-nitro-4-chloroquinoline-2-yl)-5,6,7-trichloro-1,3-tropolone was synthesized using a method for expanding the o-quinone cycle d...
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Siberian State Medical University (Tomsk)
2022-07-01
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| Series: | Бюллетень сибирской медицины |
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| Online Access: | https://bulletin.ssmu.ru/jour/article/view/4814 |
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| author | O. I. Kit V. I. Minkin E. A. Lukbanova Yu. A. Sayapin E. A. Gusakov A. O. Sitkovskaya S. Yu. Filippova E. F. Komarova A. V. Volkova D. V. Khodakova M. V. Mindar Yu. N. Lazutin M. A. Engibaryan V. E. Kolesnikov |
| author_facet | O. I. Kit V. I. Minkin E. A. Lukbanova Yu. A. Sayapin E. A. Gusakov A. O. Sitkovskaya S. Yu. Filippova E. F. Komarova A. V. Volkova D. V. Khodakova M. V. Mindar Yu. N. Lazutin M. A. Engibaryan V. E. Kolesnikov |
| author_sort | O. I. Kit |
| collection | DOAJ |
| description | The aim. To study the toxicity of 2-(6,8-dimethyl-5-nitro-4-chloroquinoline-2-yl)-5,6,7-trichloro-1,3-tropolone in vitro and in vivo.Materials and methods. 2-(6,8-dimethyl-5-nitro-4-chloroquinoline-2-yl)-5,6,7-trichloro-1,3-tropolone was synthesized using a method for expanding the o-quinone cycle during the reaction between 5-nitro-2,6,8-trimethyl4-chloroquinoline and 3,4,5,6-tetrachloro-1,2-benzoquinone while boiled in dioxane. An in vitro experiment was carried out in the human A549 cell line. Cell viability was assessed using the MTT colorimetric assay by reducing the optical density of the experimental samples compared with the control ones. Acute toxicity was studied on 20 BALB/c Nude male mice. The test compound was administered once orally as a suspension in 1% starch gel at three doses: 0.0055 (group 1), 0.055 (group 2) and 0.55 mg / g (group 3). The control group (group 4) received a placebo.Results. We synthesized a new compound, 2-(6,8-dimethyl-5-nitro-4-chloroquinoline-2-yl)-5,6,7-trichloro-1,3-tropolone. Its structure was established by 1 H nuclear magnetic resonance (NMR), infrared (IR) spectroscopy, and mass spectrometry. The yield was 19.8 g (52%), the melting point was 205–207 ºС, bright yellow crystals (benzene) were observed. The half-maximal inhibitory concentration (IC50) of 2-(6,8-dimethyl-5-nitro-4-chloroquinoline-2-yl)-5,6,7-trichloro-1,3-tropolone was 0.21 ± 0.01 μM, which was significantly lower (р < 0.05) than the IC50 of cisplatin (3.84 ± 0.23). Following the in vivo experiment, no toxic effect of tropolone was detected when administered once at a dose of 0.0055, 0.055, and 0.55 mg / g. Conclusion. 2-(6,8-dimethyl-5-nitro-4-chloroquinoline-2-yl)-5,6,7-trichloro-1,3-tropolone demonstrated cytotoxic effects on the A549 cell line at a lower IC50 than cisplatin which is widely used in treatment of cancers, including lung cancer. Insolubility of 2-(6,8-dimethyl-5-nitro-4-chloroquinoline-2-yl)-5,6,7-trichloro-1,3-tropolone in water and the absence of its toxic effect in the studied modes determine the scope of its application for further study of cumulative and antitumor effects. |
| format | Article |
| id | doaj-art-30f94e7c9b874e1d94d06d3d95a99e9f |
| institution | Matheson Library |
| issn | 1682-0363 1819-3684 |
| language | English |
| publishDate | 2022-07-01 |
| publisher | Siberian State Medical University (Tomsk) |
| record_format | Article |
| series | Бюллетень сибирской медицины |
| spelling | doaj-art-30f94e7c9b874e1d94d06d3d95a99e9f2025-08-04T16:45:44ZengSiberian State Medical University (Tomsk)Бюллетень сибирской медицины1682-03631819-36842022-07-01212606610.20538/1682-0363-2022-2-60-662890Evaluation of the cytotoxic activity and toxicity of a tropolone derivative with a potential antitumor effectO. I. Kit0V. I. Minkin1E. A. Lukbanova2Yu. A. Sayapin3E. A. Gusakov4A. O. Sitkovskaya5S. Yu. Filippova6E. F. Komarova7A. V. Volkova8D. V. Khodakova9M. V. Mindar10Yu. N. Lazutin11M. A. Engibaryan12V. E. Kolesnikov13National Medical Research Center of OncologyResearch Institute of Physical and Organic Chemistry, Southern Federal University; Southern Scientific Center of the Russian Academy of SciencesNational Medical Research Center of OncologySouthern Scientific Center of the Russian Academy of SciencesResearch Institute of Physical and Organic Chemistry, Southern Federal UniversityNational Medical Research Center of OncologyNational Medical Research Center of OncologyNational Medical Research Center of Oncology; Rostov State Medical UniversityNational Medical Research Center of OncologyNational Medical Research Center of OncologyNational Medical Research Center of OncologyNational Medical Research Center of OncologyNational Medical Research Center of OncologyNational Medical Research Center of OncologyThe aim. To study the toxicity of 2-(6,8-dimethyl-5-nitro-4-chloroquinoline-2-yl)-5,6,7-trichloro-1,3-tropolone in vitro and in vivo.Materials and methods. 2-(6,8-dimethyl-5-nitro-4-chloroquinoline-2-yl)-5,6,7-trichloro-1,3-tropolone was synthesized using a method for expanding the o-quinone cycle during the reaction between 5-nitro-2,6,8-trimethyl4-chloroquinoline and 3,4,5,6-tetrachloro-1,2-benzoquinone while boiled in dioxane. An in vitro experiment was carried out in the human A549 cell line. Cell viability was assessed using the MTT colorimetric assay by reducing the optical density of the experimental samples compared with the control ones. Acute toxicity was studied on 20 BALB/c Nude male mice. The test compound was administered once orally as a suspension in 1% starch gel at three doses: 0.0055 (group 1), 0.055 (group 2) and 0.55 mg / g (group 3). The control group (group 4) received a placebo.Results. We synthesized a new compound, 2-(6,8-dimethyl-5-nitro-4-chloroquinoline-2-yl)-5,6,7-trichloro-1,3-tropolone. Its structure was established by 1 H nuclear magnetic resonance (NMR), infrared (IR) spectroscopy, and mass spectrometry. The yield was 19.8 g (52%), the melting point was 205–207 ºС, bright yellow crystals (benzene) were observed. The half-maximal inhibitory concentration (IC50) of 2-(6,8-dimethyl-5-nitro-4-chloroquinoline-2-yl)-5,6,7-trichloro-1,3-tropolone was 0.21 ± 0.01 μM, which was significantly lower (р < 0.05) than the IC50 of cisplatin (3.84 ± 0.23). Following the in vivo experiment, no toxic effect of tropolone was detected when administered once at a dose of 0.0055, 0.055, and 0.55 mg / g. Conclusion. 2-(6,8-dimethyl-5-nitro-4-chloroquinoline-2-yl)-5,6,7-trichloro-1,3-tropolone demonstrated cytotoxic effects on the A549 cell line at a lower IC50 than cisplatin which is widely used in treatment of cancers, including lung cancer. Insolubility of 2-(6,8-dimethyl-5-nitro-4-chloroquinoline-2-yl)-5,6,7-trichloro-1,3-tropolone in water and the absence of its toxic effect in the studied modes determine the scope of its application for further study of cumulative and antitumor effects.https://bulletin.ssmu.ru/jour/article/view/4814tropolonesantitumor effect4 human non-small-cell lung cancer а549 cell linemtt assay |
| spellingShingle | O. I. Kit V. I. Minkin E. A. Lukbanova Yu. A. Sayapin E. A. Gusakov A. O. Sitkovskaya S. Yu. Filippova E. F. Komarova A. V. Volkova D. V. Khodakova M. V. Mindar Yu. N. Lazutin M. A. Engibaryan V. E. Kolesnikov Evaluation of the cytotoxic activity and toxicity of a tropolone derivative with a potential antitumor effect Бюллетень сибирской медицины tropolones antitumor effect4 human non-small-cell lung cancer а549 cell line mtt assay |
| title | Evaluation of the cytotoxic activity and toxicity of a tropolone derivative with a potential antitumor effect |
| title_full | Evaluation of the cytotoxic activity and toxicity of a tropolone derivative with a potential antitumor effect |
| title_fullStr | Evaluation of the cytotoxic activity and toxicity of a tropolone derivative with a potential antitumor effect |
| title_full_unstemmed | Evaluation of the cytotoxic activity and toxicity of a tropolone derivative with a potential antitumor effect |
| title_short | Evaluation of the cytotoxic activity and toxicity of a tropolone derivative with a potential antitumor effect |
| title_sort | evaluation of the cytotoxic activity and toxicity of a tropolone derivative with a potential antitumor effect |
| topic | tropolones antitumor effect4 human non-small-cell lung cancer а549 cell line mtt assay |
| url | https://bulletin.ssmu.ru/jour/article/view/4814 |
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