Antiproliferative and genotoxic potential of xanthen-3-one derivatives
Twelve previously synthesized, biologically active 2,6,7-trihydroxyxanthen-3-one derivatives were evaluated in vitro for antiproliferative activity. Compounds were screened against HeLa, SW620, HepG2 and A549 tumor cell lines. Compound with the trifluormethyl group on C-4’ position of the phenyl rin...
| Main Authors: | , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Sciendo
2019-12-01
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| Series: | Acta Pharmaceutica |
| Subjects: | |
| Online Access: | https://doi.org/10.2478/acph-2019-0044 |
| _version_ | 1819020122258407424 |
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| author | Veljović Elma Špirtović-Halilović Selma Muratović Samija Osmanović Amar Haverić Sanin Haverić Anja Hadžić Maida Salihović Mirsada Malenica Maja Šapčanin Aida Završnik Davorka |
| author_facet | Veljović Elma Špirtović-Halilović Selma Muratović Samija Osmanović Amar Haverić Sanin Haverić Anja Hadžić Maida Salihović Mirsada Malenica Maja Šapčanin Aida Završnik Davorka |
| author_sort | Veljović Elma |
| collection | DOAJ |
| description | Twelve previously synthesized, biologically active 2,6,7-trihydroxyxanthen-3-one derivatives were evaluated in vitro for antiproliferative activity. Compounds were screened against HeLa, SW620, HepG2 and A549 tumor cell lines. Compound with the trifluormethyl group on C-4’ position of the phenyl ring showed the best inhibitory activity towards HeLa and A549 tumor cells with IC50 of 0.7 and 4.1 µmol L−1, resp. Compound with chlorine and fluorine substituents on aryl ring showed the best antiproliferative activity against SW620 with IC50 of 4.1 µmol L–1 and against HepG2 tumor cell line with IC50 of 4.2 µmol L–1. Analyses of cytotoxic and genotoxic potential of the trifluormethyl derivative were performed with cytokinesis-block micronucleus cytome assay in human lymphocyte culture and revealed no genotoxic and cytotoxic effects. The most potent compounds were subjected to molecular docking simulations in order to analyse bindings to molecular targets and, at the same time, further support the results of experimental cytotoxic tests. Docking studies showed sites of importance in forming hydrogen bonds of the most potent compounds with targets of interest. |
| first_indexed | 2024-12-21T03:46:11Z |
| format | Article |
| id | doaj.art-5deedca75be64b6da425bd97d384457c |
| institution | Directory Open Access Journal |
| issn | 1846-9558 |
| language | English |
| last_indexed | 2024-12-21T03:46:11Z |
| publishDate | 2019-12-01 |
| publisher | Sciendo |
| record_format | Article |
| series | Acta Pharmaceutica |
| spelling | doaj.art-5deedca75be64b6da425bd97d384457c2022-12-21T19:17:05ZengSciendoActa Pharmaceutica1846-95582019-12-0169468369410.2478/acph-2019-0044acph-2019-0044Antiproliferative and genotoxic potential of xanthen-3-one derivativesVeljović Elma0Špirtović-Halilović Selma1Muratović Samija2Osmanović Amar3Haverić Sanin4Haverić Anja5Hadžić Maida6Salihović Mirsada7Malenica Maja8Šapčanin Aida9Završnik Davorka10University of Sarajevo, Faculty of Pharmacy, 71000Sarajevo, Bosnia and HerzegovinaUniversity of Sarajevo, Faculty of Pharmacy, 71000Sarajevo, Bosnia and HerzegovinaUniversity of Sarajevo, Faculty of Pharmacy, 71000Sarajevo, Bosnia and HerzegovinaUniversity of Sarajevo, Faculty of Pharmacy, 71000Sarajevo, Bosnia and HerzegovinaUniversity of Sarajevo, Institute for Genetic Engineering and Biotechnology71000Sarajevo, Bosnia and HerzegovinaUniversity of Sarajevo, Institute for Genetic Engineering and Biotechnology71000Sarajevo, Bosnia and HerzegovinaUniversity of Sarajevo, Institute for Genetic Engineering and Biotechnology71000Sarajevo, Bosnia and HerzegovinaUniversity of Sarajevo, Faculty of Pharmacy, 71000Sarajevo, Bosnia and HerzegovinaUniversity of Sarajevo, Faculty of Pharmacy, 71000Sarajevo, Bosnia and HerzegovinaUniversity of Sarajevo, Faculty of Pharmacy, 71000Sarajevo, Bosnia and HerzegovinaUniversity of Sarajevo, Faculty of Pharmacy, 71000Sarajevo, Bosnia and HerzegovinaTwelve previously synthesized, biologically active 2,6,7-trihydroxyxanthen-3-one derivatives were evaluated in vitro for antiproliferative activity. Compounds were screened against HeLa, SW620, HepG2 and A549 tumor cell lines. Compound with the trifluormethyl group on C-4’ position of the phenyl ring showed the best inhibitory activity towards HeLa and A549 tumor cells with IC50 of 0.7 and 4.1 µmol L−1, resp. Compound with chlorine and fluorine substituents on aryl ring showed the best antiproliferative activity against SW620 with IC50 of 4.1 µmol L–1 and against HepG2 tumor cell line with IC50 of 4.2 µmol L–1. Analyses of cytotoxic and genotoxic potential of the trifluormethyl derivative were performed with cytokinesis-block micronucleus cytome assay in human lymphocyte culture and revealed no genotoxic and cytotoxic effects. The most potent compounds were subjected to molecular docking simulations in order to analyse bindings to molecular targets and, at the same time, further support the results of experimental cytotoxic tests. Docking studies showed sites of importance in forming hydrogen bonds of the most potent compounds with targets of interest.https://doi.org/10.2478/acph-2019-0044antiproliferative activitygenotoxic potentialdocking studyxanthen-3-one derivativescytokinesis-block micronucleus cytome assay |
| spellingShingle | Veljović Elma Špirtović-Halilović Selma Muratović Samija Osmanović Amar Haverić Sanin Haverić Anja Hadžić Maida Salihović Mirsada Malenica Maja Šapčanin Aida Završnik Davorka Antiproliferative and genotoxic potential of xanthen-3-one derivatives Acta Pharmaceutica antiproliferative activity genotoxic potential docking study xanthen-3-one derivatives cytokinesis-block micronucleus cytome assay |
| title | Antiproliferative and genotoxic potential of xanthen-3-one derivatives |
| title_full | Antiproliferative and genotoxic potential of xanthen-3-one derivatives |
| title_fullStr | Antiproliferative and genotoxic potential of xanthen-3-one derivatives |
| title_full_unstemmed | Antiproliferative and genotoxic potential of xanthen-3-one derivatives |
| title_short | Antiproliferative and genotoxic potential of xanthen-3-one derivatives |
| title_sort | antiproliferative and genotoxic potential of xanthen 3 one derivatives |
| topic | antiproliferative activity genotoxic potential docking study xanthen-3-one derivatives cytokinesis-block micronucleus cytome assay |
| url | https://doi.org/10.2478/acph-2019-0044 |
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