Synthesis and anticancer properties of 1-(2-isopropyl-5-methylphenoxymethyl)-3R-4-aryl-5,6,7,8-tetrahydro-2,2а,8а-triazacyclopenta[cd]azulene derivatives
In recent years, attention to itself is attracted to the problem of treatment of cancer that is caused by increase in patients, especially of working age. Therefore, the enlargement of the arsenal of anticancer medicines of a wide spectrum of action is actual. The purpose of the study was to synt...
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| Format: | Article |
| Language: | Ukrainian |
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The State Expert Center of the Ministry of Health of Ukraine
2018-08-01
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| Series: | Фармацевтичний журнал |
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| Online Access: | https://pharmj.org.ua/index.php/journal/article/view/14/12 |
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| author | S. A. Demchenko A. E. Dudnik T. A. Bukhtiarova L. S. Bobkova A. M. Demchenko |
| author_facet | S. A. Demchenko A. E. Dudnik T. A. Bukhtiarova L. S. Bobkova A. M. Demchenko |
| author_sort | S. A. Demchenko |
| collection | DOAJ |
| description | In recent years, attention to itself is attracted to the problem of treatment of cancer that is caused by increase in patients, especially of working age. Therefore, the enlargement of the arsenal of anticancer medicines of a wide spectrum of action is actual.
The purpose of the study was to synthesize substances with potentially antitumor properties in a series 1-(2-isopropyl-5-methylphenoxymethyl)-3R-4-aryl-5,6,7,8-tetrahydro-2,2а,8а-triazacyclopenta[cd]azulene derivatives and to study the effect of synthesized compounds on inhibition of growth (or their destruction) of a wide range of cancer.
The objects of the study were derivatives of 1-(2-isopropyl-5-methylphenoxymethyl)-3R-4-aryl-5,6,7,8-tetrahydro-2,2а,8а-triazacyclopenta[cd]azulene, which were synthesized by refluxing 3-(2-isopropyl-5-methylphenoxymethyl)-6,7,8,9-tetrahydro-5Н-[1,2,4]triazolo[4,3-a]azepine with с appropriate α-halogenketones in ethyl acetate and further cyclization in an alkaline medium. Использовали данные NMR 1Н spectroscopy data were used. The primary evaluation of anticancer activity was carried out National Cancer Institute of Health, USA within the Development Therapeutic Program.
A series of new of 1-(2-isopropyl-5-methylphenoxymethyl)-3R-4-aryl-5,6,7,8-tetrahydro-2,2а,8а-triazacyclopenta[cd]azulene derivatives was synthesized, their structure and purity were confirmed by NMR 1Н spectroscopy. The anticancer activity of the synthesized compounds was studied both at a concentration of 10-5 mol/l and in a concentration gradient of 10-4‒10-8 mol/l in experiments in vivo on cancer cell lines. It is shown that insertion of methyl group into position 3 of heterocyclic system of the basic structure of 4-aryl-5,6,7,8-tetrahydro-2,2a,8a-triazacyclopenta[cd]azulene leads to an increase in the anticancer effect.
It is found that the tested compounds showed high anticancer effect on all types of cancer cell lines investigated – leukemia, non-small cell lung cancer, colon cancer, CNS cancer, melanoma, ovarian cancer, renal cancer, prostate cancer and breast cancer. |
| first_indexed | 2024-12-17T06:36:45Z |
| format | Article |
| id | doaj.art-437857b8a6a24c17ab188c59d2cb8f08 |
| institution | Directory Open Access Journal |
| issn | 0367-3057 2617-9628 |
| language | Ukrainian |
| last_indexed | 2024-12-17T06:36:45Z |
| publishDate | 2018-08-01 |
| publisher | The State Expert Center of the Ministry of Health of Ukraine |
| record_format | Article |
| series | Фармацевтичний журнал |
| spelling | doaj.art-437857b8a6a24c17ab188c59d2cb8f082022-12-21T21:59:58ZukrThe State Expert Center of the Ministry of Health of UkraineФармацевтичний журнал0367-30572617-96282018-08-01(1-2)516010.32352/0367-3057.1-2.18.06Synthesis and anticancer properties of 1-(2-isopropyl-5-methylphenoxymethyl)-3R-4-aryl-5,6,7,8-tetrahydro-2,2а,8а-triazacyclopenta[cd]azulene derivativesS. A. Demchenko0A. E. Dudnik1T. A. Bukhtiarova2L. S. Bobkova3A. M. Demchenko4SI «Institute of Pharmacology and Toxicology of the National Academy of Medical Sciences of Ukraine», KyivSI «Institute of Pharmacology and Toxicology of the National Academy of Medical Sciences of Ukraine», KyivSI «Institute of Pharmacology and Toxicology of the National Academy of Medical Sciences of Ukraine», KyivSI «Institute of Pharmacology and Toxicology of the National Academy of Medical Sciences of Ukraine», KyivSI «Institute of Pharmacology and Toxicology of the National Academy of Medical Sciences of Ukraine», KyivIn recent years, attention to itself is attracted to the problem of treatment of cancer that is caused by increase in patients, especially of working age. Therefore, the enlargement of the arsenal of anticancer medicines of a wide spectrum of action is actual. The purpose of the study was to synthesize substances with potentially antitumor properties in a series 1-(2-isopropyl-5-methylphenoxymethyl)-3R-4-aryl-5,6,7,8-tetrahydro-2,2а,8а-triazacyclopenta[cd]azulene derivatives and to study the effect of synthesized compounds on inhibition of growth (or their destruction) of a wide range of cancer. The objects of the study were derivatives of 1-(2-isopropyl-5-methylphenoxymethyl)-3R-4-aryl-5,6,7,8-tetrahydro-2,2а,8а-triazacyclopenta[cd]azulene, which were synthesized by refluxing 3-(2-isopropyl-5-methylphenoxymethyl)-6,7,8,9-tetrahydro-5Н-[1,2,4]triazolo[4,3-a]azepine with с appropriate α-halogenketones in ethyl acetate and further cyclization in an alkaline medium. Использовали данные NMR 1Н spectroscopy data were used. The primary evaluation of anticancer activity was carried out National Cancer Institute of Health, USA within the Development Therapeutic Program. A series of new of 1-(2-isopropyl-5-methylphenoxymethyl)-3R-4-aryl-5,6,7,8-tetrahydro-2,2а,8а-triazacyclopenta[cd]azulene derivatives was synthesized, their structure and purity were confirmed by NMR 1Н spectroscopy. The anticancer activity of the synthesized compounds was studied both at a concentration of 10-5 mol/l and in a concentration gradient of 10-4‒10-8 mol/l in experiments in vivo on cancer cell lines. It is shown that insertion of methyl group into position 3 of heterocyclic system of the basic structure of 4-aryl-5,6,7,8-tetrahydro-2,2a,8a-triazacyclopenta[cd]azulene leads to an increase in the anticancer effect. It is found that the tested compounds showed high anticancer effect on all types of cancer cell lines investigated – leukemia, non-small cell lung cancer, colon cancer, CNS cancer, melanoma, ovarian cancer, renal cancer, prostate cancer and breast cancer.https://pharmj.org.ua/index.php/journal/article/view/14/1222а8а-triazacyclopenta[cd]azulenescondensation(2-isopropyl-5-methylphenoxy)acetic acid hydrazideanticancer activity |
| spellingShingle | S. A. Demchenko A. E. Dudnik T. A. Bukhtiarova L. S. Bobkova A. M. Demchenko Synthesis and anticancer properties of 1-(2-isopropyl-5-methylphenoxymethyl)-3R-4-aryl-5,6,7,8-tetrahydro-2,2а,8а-triazacyclopenta[cd]azulene derivatives Фармацевтичний журнал 2 2а 8а-triazacyclopenta[cd]azulenes condensation (2-isopropyl-5-methylphenoxy)acetic acid hydrazide anticancer activity |
| title | Synthesis and anticancer properties of 1-(2-isopropyl-5-methylphenoxymethyl)-3R-4-aryl-5,6,7,8-tetrahydro-2,2а,8а-triazacyclopenta[cd]azulene derivatives |
| title_full | Synthesis and anticancer properties of 1-(2-isopropyl-5-methylphenoxymethyl)-3R-4-aryl-5,6,7,8-tetrahydro-2,2а,8а-triazacyclopenta[cd]azulene derivatives |
| title_fullStr | Synthesis and anticancer properties of 1-(2-isopropyl-5-methylphenoxymethyl)-3R-4-aryl-5,6,7,8-tetrahydro-2,2а,8а-triazacyclopenta[cd]azulene derivatives |
| title_full_unstemmed | Synthesis and anticancer properties of 1-(2-isopropyl-5-methylphenoxymethyl)-3R-4-aryl-5,6,7,8-tetrahydro-2,2а,8а-triazacyclopenta[cd]azulene derivatives |
| title_short | Synthesis and anticancer properties of 1-(2-isopropyl-5-methylphenoxymethyl)-3R-4-aryl-5,6,7,8-tetrahydro-2,2а,8а-triazacyclopenta[cd]azulene derivatives |
| title_sort | synthesis and anticancer properties of 1 2 isopropyl 5 methylphenoxymethyl 3r 4 aryl 5 6 7 8 tetrahydro 2 2а 8а triazacyclopenta cd azulene derivatives |
| topic | 2 2а 8а-triazacyclopenta[cd]azulenes condensation (2-isopropyl-5-methylphenoxy)acetic acid hydrazide anticancer activity |
| url | https://pharmj.org.ua/index.php/journal/article/view/14/12 |
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