A New Concept of Enhancing the Anticancer Activity of Manganese Terpyridine Complex by Oxygen-Containing Substituent Modification
Eleven manganese 4′-substituted-2,2′:6′,2″-terpyridine complexes (<b>1a</b>–<b>1c</b> and <b>2a</b>–<b>2h</b>) with three non-oxygen-containing substituents (<b>L<sup>1a</sup></b>–<b>L<sup>1c</sup></b>: p...
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MDPI AG
2023-02-01
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| Online Access: | https://www.mdpi.com/1422-0067/24/4/3903 |
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| author | Jiahe Li Min Chen Jinzhang Jiang Jieyou Huang Hailan Chen Lixia Pan Dmytro S. Nesterov Zhen Ma Armando J. L. Pombeiro |
| author_facet | Jiahe Li Min Chen Jinzhang Jiang Jieyou Huang Hailan Chen Lixia Pan Dmytro S. Nesterov Zhen Ma Armando J. L. Pombeiro |
| author_sort | Jiahe Li |
| collection | DOAJ |
| description | Eleven manganese 4′-substituted-2,2′:6′,2″-terpyridine complexes (<b>1a</b>–<b>1c</b> and <b>2a</b>–<b>2h</b>) with three non-oxygen-containing substituents (<b>L<sup>1a</sup></b>–<b>L<sup>1c</sup></b>: phenyl, naphthalen-2-yl and naphthalen-1-yl, <b>L<sup>1a</sup></b>–<b>L<sup>1c</sup></b>) and eight oxygen-containing substituents (<b>L<sup>2a</sup></b>–<b>L<sup>2h</sup></b>: 4-hydroxyl-phenyl, 3-hydroxyl-phenyl, 2-hydroxyl-phenyl, 4-methoxyl-phenyl, 4-carboxyl-phenyl, 4-(methylsulfonyl)phenyl, 4-nitrophenyl and furan-2-yl) were prepared and characterized by IR, elemental analysis or single crystal X-ray diffraction. In vitro data demonstrate that all of these show higher antiproliferative activities than cisplatin against five human carcinoma cell lines: A549, Bel-7402, Eca-109, HeLa and MCF-7. Compound <b>2d</b> presents the strongest antiproliferative effect against A549 and HeLa cells, with IC<sub>50</sub> values being 0.281 μM and 0.356 μM, respectively. The lowest IC<sub>50</sub> values against Bel-7402 (0.523 μM) Eca-109 (0.514 μM) and MCF-7 (0.356 μM) were obtained for compounds <b>2h</b>, <b>2g</b> and <b>2c</b>, respectively. Compound <b>2g</b> with a nitro group showed the best results on the whole, with relevantly low IC<sub>50</sub> values against all the tested tumor cells. The DNA interactions with these compounds were studied by circular dichroism spectroscopic and molecular modeling methods. Spectrophotometric results revealed that the compounds have strong affinities in binding with DNA as intercalators, and the binding induces DNA conformational transition. Molecular docking studies indicate that the binding is contributed by the π–π stacking and hydrogen bonds. The anticancer activities of the compounds are correlated with their DNA binding ability, and the modification of oxygen-containing substituents significantly enhanced the anticancer activity, which could provide a new rationale for the future design of terpyridine-based metal complexes with antitumor potential. |
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| spelling | doaj.art-da3e3b0e4cc448bca82e7288e004740b2023-11-16T21:06:42ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672023-02-01244390310.3390/ijms24043903A New Concept of Enhancing the Anticancer Activity of Manganese Terpyridine Complex by Oxygen-Containing Substituent ModificationJiahe Li0Min Chen1Jinzhang Jiang2Jieyou Huang3Hailan Chen4Lixia Pan5Dmytro S. Nesterov6Zhen Ma7Armando J. L. Pombeiro8School of Chemistry and Chemical Engineering, Guangxi University, Nanning 530004, ChinaSchool of Chemistry and Chemical Engineering, Guangxi University, Nanning 530004, ChinaSchool of Chemistry and Chemical Engineering, Guangxi University, Nanning 530004, ChinaSchool of Chemistry and Chemical Engineering, Guangxi University, Nanning 530004, ChinaSchool of Animal Science and Technology, Guangxi University, Nanning 530004, ChinaNational Engineering Research Center for Non-Food Biorefinery, State Key Laboratory of Non-Food Biomass and Enzyme Technology, Guangxi Academy of Sciences, Nanning 530007, ChinaCentro de Química Estrutural, Institute of Molecular Sciences, Instituto Superior Técnico, Universidade de Lisboa, 1049-001 Lisbon, PortugalSchool of Chemistry and Chemical Engineering, Guangxi University, Nanning 530004, ChinaCentro de Química Estrutural, Institute of Molecular Sciences, Instituto Superior Técnico, Universidade de Lisboa, 1049-001 Lisbon, PortugalEleven manganese 4′-substituted-2,2′:6′,2″-terpyridine complexes (<b>1a</b>–<b>1c</b> and <b>2a</b>–<b>2h</b>) with three non-oxygen-containing substituents (<b>L<sup>1a</sup></b>–<b>L<sup>1c</sup></b>: phenyl, naphthalen-2-yl and naphthalen-1-yl, <b>L<sup>1a</sup></b>–<b>L<sup>1c</sup></b>) and eight oxygen-containing substituents (<b>L<sup>2a</sup></b>–<b>L<sup>2h</sup></b>: 4-hydroxyl-phenyl, 3-hydroxyl-phenyl, 2-hydroxyl-phenyl, 4-methoxyl-phenyl, 4-carboxyl-phenyl, 4-(methylsulfonyl)phenyl, 4-nitrophenyl and furan-2-yl) were prepared and characterized by IR, elemental analysis or single crystal X-ray diffraction. In vitro data demonstrate that all of these show higher antiproliferative activities than cisplatin against five human carcinoma cell lines: A549, Bel-7402, Eca-109, HeLa and MCF-7. Compound <b>2d</b> presents the strongest antiproliferative effect against A549 and HeLa cells, with IC<sub>50</sub> values being 0.281 μM and 0.356 μM, respectively. The lowest IC<sub>50</sub> values against Bel-7402 (0.523 μM) Eca-109 (0.514 μM) and MCF-7 (0.356 μM) were obtained for compounds <b>2h</b>, <b>2g</b> and <b>2c</b>, respectively. Compound <b>2g</b> with a nitro group showed the best results on the whole, with relevantly low IC<sub>50</sub> values against all the tested tumor cells. The DNA interactions with these compounds were studied by circular dichroism spectroscopic and molecular modeling methods. Spectrophotometric results revealed that the compounds have strong affinities in binding with DNA as intercalators, and the binding induces DNA conformational transition. Molecular docking studies indicate that the binding is contributed by the π–π stacking and hydrogen bonds. The anticancer activities of the compounds are correlated with their DNA binding ability, and the modification of oxygen-containing substituents significantly enhanced the anticancer activity, which could provide a new rationale for the future design of terpyridine-based metal complexes with antitumor potential.https://www.mdpi.com/1422-0067/24/4/3903terpyridinemanganese complexanticancer activityDNA interactionmolecular docking |
| spellingShingle | Jiahe Li Min Chen Jinzhang Jiang Jieyou Huang Hailan Chen Lixia Pan Dmytro S. Nesterov Zhen Ma Armando J. L. Pombeiro A New Concept of Enhancing the Anticancer Activity of Manganese Terpyridine Complex by Oxygen-Containing Substituent Modification International Journal of Molecular Sciences terpyridine manganese complex anticancer activity DNA interaction molecular docking |
| title | A New Concept of Enhancing the Anticancer Activity of Manganese Terpyridine Complex by Oxygen-Containing Substituent Modification |
| title_full | A New Concept of Enhancing the Anticancer Activity of Manganese Terpyridine Complex by Oxygen-Containing Substituent Modification |
| title_fullStr | A New Concept of Enhancing the Anticancer Activity of Manganese Terpyridine Complex by Oxygen-Containing Substituent Modification |
| title_full_unstemmed | A New Concept of Enhancing the Anticancer Activity of Manganese Terpyridine Complex by Oxygen-Containing Substituent Modification |
| title_short | A New Concept of Enhancing the Anticancer Activity of Manganese Terpyridine Complex by Oxygen-Containing Substituent Modification |
| title_sort | new concept of enhancing the anticancer activity of manganese terpyridine complex by oxygen containing substituent modification |
| topic | terpyridine manganese complex anticancer activity DNA interaction molecular docking |
| url | https://www.mdpi.com/1422-0067/24/4/3903 |
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