Mitochondria-Targeting Click-Derived Pyridinyltriazolylmethylquinoxaline-Based Y-Shaped Binuclear Luminescent Ruthenium(II) and Iridium(III) Complexes as Cancer Theranostic Agents
| Autor: | Suban K. Sahoo, Bipasha Bose, Seshu Varddhan, Priyankar Paira, Debashis Panda, Nilmadhab Roy, Utsav Sen, Venkatesan Muthukumar, Yukti Madaan |
|---|---|
| Rok vydání: | 2020 |
| Předmět: |
Theranostic Nanomedicine
Pyridines Cell Antineoplastic Agents Mitochondrion 010402 general chemistry Iridium 01 natural sciences Ruthenium Inorganic Chemistry HeLa Structure-Activity Relationship Quinoxalines medicine Humans Physical and Theoretical Chemistry Cell Proliferation Cisplatin Luminescent Agents biology Dose-Response Relationship Drug Molecular Structure 010405 organic chemistry Chemistry HEK 293 cells Cancer Cell Cycle Checkpoints medicine.disease biology.organism_classification 0104 chemical sciences Mitochondria medicine.anatomical_structure HEK293 Cells Cancer cell Cancer research Drug Screening Assays Antitumor medicine.drug |
| Zdroj: | Inorganic chemistry. 59(23) |
| ISSN: | 1520-510X |
| Popis: | Due to several negative issues, market available drugs have been gradually losing their importance in the treatment of cancer. With a view to discover suitable drugs capable of diagnosing as well as inhibiting the growth of cancer cells, we have aspired to develop a group of theranostic metal complexes which will be (i) target specific, (ii) cytoselective, thus rendering the normal cell unaffected, (iii) water-soluble, (iv) cancer cell permeable, and (v) luminescent, being beneficial for healing the cancer eternally. Therefore, to reach our goal, we have prepared novel Ru(II)- and Ir(III)-based bimetallic and hetero bimetallic scaffolds using click-derived pyridinyltriazolylmethylquinoxaline ligands followed by metal coordination. Most of the compounds have displayed significant cytoselectivity against colorectal adenocarcinoma (Caco-2) and epithiloid cervical carcinoma (HeLa) cells with respect to normal human embryonic kidney cells (HEK-293) compared to cisplatin [cis-diamminedichloroplatinum(II)] along with excellent binding efficacy with DNA as well as serum albumin. Complex [(η6-p-cymene)(η5-Cp*)RuIIIrIIICl2(K2-N,N-L)](PF6)2 [RuIrL] exhibited the best cytoselectivity against all the human cancer cells and was identified as the most significant cancer theranostic agent in terms of potency, selectivity, and fluorescence quantum yield. Investigation of the localization of complex [Ir2L] and [RuIrL] in the more aggressive colorectal adenocarcinoma cell HT-29 indicates that mitochondria are the key cellular target for destroying cancer cells. Mitochondrial dysfunction and G2/M phase cell cycle arrest in HT-29 cell were found to be involved in the apoptotic cell death pathway induced by the test complexes [Ir2L] and [RuIrL]. These results validate the concept that these types of complexes will be reasonably able to exert great potential for tumor diagnosis as well as therapy in the near future. |
| Databáze: | OpenAIRE |
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