Novel Tl(III) complexes containing pyridine-2,6-dicarboxylate derivatives with selective anticancer activity through inducing mitochondria-mediated apoptosis in A375 cells
Abstract Three novel Tl(III) complexes (C1), (C2) and (C3) were synthesized using the one-pot reactions of pyridine dicarboxylic acid derivatives, 2-aminobenzimidazole and/or 4-aminopyridine, and also thallium(III) nitrate trihydrate metal salt. The structure of all three complexes was determined by...
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| Format: | Article |
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Nature Portfolio
2021-08-01
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| Series: | Scientific Reports |
| Online Access: | https://doi.org/10.1038/s41598-021-95278-y |
| _version_ | 1818997200016900096 |
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| author | Sara Abdolmaleki Mohammad Ghadermazi Alireza Aliabadi |
| author_facet | Sara Abdolmaleki Mohammad Ghadermazi Alireza Aliabadi |
| author_sort | Sara Abdolmaleki |
| collection | DOAJ |
| description | Abstract Three novel Tl(III) complexes (C1), (C2) and (C3) were synthesized using the one-pot reactions of pyridine dicarboxylic acid derivatives, 2-aminobenzimidazole and/or 4-aminopyridine, and also thallium(III) nitrate trihydrate metal salt. The structure of all three complexes was determined by the single-crystal X-ray diffraction. C1 and C2 were realized to be isostructural with disordered square anti-prismatic geometry and for C3 arrangement of the distorted tricapped triangular prism was proposed. Cyclic voltammetry measurements on the complexes exhibited that formal potential values are more positive for C1 (E0ˊ 0.109 V) and C3 (E0ˊ 0.244 V) compared to C2 (E0ˊ –0.051 V), versus Ag/AgCl under argon. Moreover, cytotoxicity of the compounds was evaluated in vitro against two cancer cell lines including a human melanoma (A375), a human colon adenocarcinoma (HT29), and also one normal cell human foreskin fibroblast (HFF). The selective and potent cytotoxicity effect was exhibited by C1 and C3 on cancer cell lines. The apoptosis through a caspase-dependent mitochondrion pathway was confirmed by ROS production, MMP reduction, p53 activation, Bax up-regulation, and Bcl-2 down-regulation, cytochrome c release, procaspase-9, and 3 expression, for A375 cells treated to C1 and C3. According to similar cellular uptake of the complexes in A375 cell line, the generation of ROS was considered as an effective agent to justify the inhibition effect C1 and C3 on mentioned cells. Furthermore, arresting the cell cycle in the G2-M phase and inducing apoptosis were indicated by these two complexes. |
| first_indexed | 2024-12-20T21:41:51Z |
| format | Article |
| id | doaj.art-ebef2d8a94bb4cf8965895d913191886 |
| institution | Directory Open Access Journal |
| issn | 2045-2322 |
| language | English |
| last_indexed | 2024-12-20T21:41:51Z |
| publishDate | 2021-08-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Scientific Reports |
| spelling | doaj.art-ebef2d8a94bb4cf8965895d9131918862022-12-21T19:25:48ZengNature PortfolioScientific Reports2045-23222021-08-0111111510.1038/s41598-021-95278-yNovel Tl(III) complexes containing pyridine-2,6-dicarboxylate derivatives with selective anticancer activity through inducing mitochondria-mediated apoptosis in A375 cellsSara Abdolmaleki0Mohammad Ghadermazi1Alireza Aliabadi2Department of Chemistry, Faculty of Science, University of KurdistanDepartment of Chemistry, Faculty of Science, University of KurdistanPharmaceutical Sciences Research Center, Health Institute, School of Pharmacy, Kermanshah University of Medical SciencesAbstract Three novel Tl(III) complexes (C1), (C2) and (C3) were synthesized using the one-pot reactions of pyridine dicarboxylic acid derivatives, 2-aminobenzimidazole and/or 4-aminopyridine, and also thallium(III) nitrate trihydrate metal salt. The structure of all three complexes was determined by the single-crystal X-ray diffraction. C1 and C2 were realized to be isostructural with disordered square anti-prismatic geometry and for C3 arrangement of the distorted tricapped triangular prism was proposed. Cyclic voltammetry measurements on the complexes exhibited that formal potential values are more positive for C1 (E0ˊ 0.109 V) and C3 (E0ˊ 0.244 V) compared to C2 (E0ˊ –0.051 V), versus Ag/AgCl under argon. Moreover, cytotoxicity of the compounds was evaluated in vitro against two cancer cell lines including a human melanoma (A375), a human colon adenocarcinoma (HT29), and also one normal cell human foreskin fibroblast (HFF). The selective and potent cytotoxicity effect was exhibited by C1 and C3 on cancer cell lines. The apoptosis through a caspase-dependent mitochondrion pathway was confirmed by ROS production, MMP reduction, p53 activation, Bax up-regulation, and Bcl-2 down-regulation, cytochrome c release, procaspase-9, and 3 expression, for A375 cells treated to C1 and C3. According to similar cellular uptake of the complexes in A375 cell line, the generation of ROS was considered as an effective agent to justify the inhibition effect C1 and C3 on mentioned cells. Furthermore, arresting the cell cycle in the G2-M phase and inducing apoptosis were indicated by these two complexes.https://doi.org/10.1038/s41598-021-95278-y |
| spellingShingle | Sara Abdolmaleki Mohammad Ghadermazi Alireza Aliabadi Novel Tl(III) complexes containing pyridine-2,6-dicarboxylate derivatives with selective anticancer activity through inducing mitochondria-mediated apoptosis in A375 cells Scientific Reports |
| title | Novel Tl(III) complexes containing pyridine-2,6-dicarboxylate derivatives with selective anticancer activity through inducing mitochondria-mediated apoptosis in A375 cells |
| title_full | Novel Tl(III) complexes containing pyridine-2,6-dicarboxylate derivatives with selective anticancer activity through inducing mitochondria-mediated apoptosis in A375 cells |
| title_fullStr | Novel Tl(III) complexes containing pyridine-2,6-dicarboxylate derivatives with selective anticancer activity through inducing mitochondria-mediated apoptosis in A375 cells |
| title_full_unstemmed | Novel Tl(III) complexes containing pyridine-2,6-dicarboxylate derivatives with selective anticancer activity through inducing mitochondria-mediated apoptosis in A375 cells |
| title_short | Novel Tl(III) complexes containing pyridine-2,6-dicarboxylate derivatives with selective anticancer activity through inducing mitochondria-mediated apoptosis in A375 cells |
| title_sort | novel tl iii complexes containing pyridine 2 6 dicarboxylate derivatives with selective anticancer activity through inducing mitochondria mediated apoptosis in a375 cells |
| url | https://doi.org/10.1038/s41598-021-95278-y |
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