Binoy Kar, Shanooja Shanavas, Arun Karmakar, Apoorva H. Nagendra, Seshu Vardhan, Suban K Sahoo, Bipasha Bose*, Subrata Kundu* and Priyankar Paira*,
{"title":"2-Aryl-1H-imidazo[4,5-f][1,10]phenanthroline-Based Binuclear Ru(II)/Ir(III)/Re(I) Complexes as Mitochondria Targeting Cancer Stem Cell Therapeutic Agents.","authors":"Binoy Kar, Shanooja Shanavas, Arun Karmakar, Apoorva H. Nagendra, Seshu Vardhan, Suban K Sahoo, Bipasha Bose*, Subrata Kundu* and Priyankar Paira*, ","doi":"10.1021/acs.jmedchem.4c00406","DOIUrl":null,"url":null,"abstract":"<p >A series of novel Ru(II)/Ir(III)/Re(I)-based organometallic complexes [<b>Ru</b><sub><b>2</b></sub><b>L1</b>, <b>Ru</b><sub><b>2</b></sub><b>L2</b>, <b>Ir</b><sub><b>2</b></sub><b>L1</b>, <b>Ir</b><sub><b>2</b></sub><b>L2</b>, <b>Re</b><sub><b>2</b></sub><b>L1</b>, and <b>Re</b><sub><b>2</b></sub><b>L2</b>] have been synthesized to assess their potency and selectivity against multiple cancer cells A549, HCT-116, and HCT-116 colon CSCs. The cytotoxic screening of the synthesized complexes has revealed that complex <b>Ru</b><sub><b>2</b></sub><b>L1</b> and <b>Ir</b><sub><b>2</b></sub><b>L2</b> are two proficient complexes among all, but <b>Ru</b><sub><b>2</b></sub><b>L1</b> is the most potent complex. A significant binding constant value was observed for DNA and BSA in all complexes. Significant lipophilic properties allow them to penetrate cancer cell membranes, and substantial quantum yield (ϕ<sub>f</sub>) values support bioimaging potential. Again, these complexes are particular for mitochondrial localization and produce a profuse amount of ROS to damage the mitochondrial DNA and then G1 phase cell-cycle arrest. Protein expression analysis unveiled that pro-apoptotic Bax protein overexpressed in <b>Ru</b><sub><b>2</b></sub><b>L1</b>-treated cells, whereas antiapoptotic Bcl-2 protein was expressed twofold in <b>Ir</b><sub><b>2</b></sub><b>L2</b>-treated cells, which correlated with autophagy reticence.</p>","PeriodicalId":46,"journal":{"name":"Journal of Medicinal Chemistry","volume":null,"pages":null},"PeriodicalIF":6.8000,"publicationDate":"2024-05-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"2-Aryl-1H-imidazo[4,5-f][1,10]phenanthroline-Based Binuclear Ru(II)/Ir(III)/Re(I) Complexes as Mitochondria Targeting Cancer Stem Cell Therapeutic Agents#\",\"authors\":\"Binoy Kar, Shanooja Shanavas, Arun Karmakar, Apoorva H. Nagendra, Seshu Vardhan, Suban K Sahoo, Bipasha Bose*, Subrata Kundu* and Priyankar Paira*, \",\"doi\":\"10.1021/acs.jmedchem.4c00406\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p >A series of novel Ru(II)/Ir(III)/Re(I)-based organometallic complexes [<b>Ru</b><sub><b>2</b></sub><b>L1</b>, <b>Ru</b><sub><b>2</b></sub><b>L2</b>, <b>Ir</b><sub><b>2</b></sub><b>L1</b>, <b>Ir</b><sub><b>2</b></sub><b>L2</b>, <b>Re</b><sub><b>2</b></sub><b>L1</b>, and <b>Re</b><sub><b>2</b></sub><b>L2</b>] have been synthesized to assess their potency and selectivity against multiple cancer cells A549, HCT-116, and HCT-116 colon CSCs. The cytotoxic screening of the synthesized complexes has revealed that complex <b>Ru</b><sub><b>2</b></sub><b>L1</b> and <b>Ir</b><sub><b>2</b></sub><b>L2</b> are two proficient complexes among all, but <b>Ru</b><sub><b>2</b></sub><b>L1</b> is the most potent complex. A significant binding constant value was observed for DNA and BSA in all complexes. Significant lipophilic properties allow them to penetrate cancer cell membranes, and substantial quantum yield (ϕ<sub>f</sub>) values support bioimaging potential. Again, these complexes are particular for mitochondrial localization and produce a profuse amount of ROS to damage the mitochondrial DNA and then G1 phase cell-cycle arrest. Protein expression analysis unveiled that pro-apoptotic Bax protein overexpressed in <b>Ru</b><sub><b>2</b></sub><b>L1</b>-treated cells, whereas antiapoptotic Bcl-2 protein was expressed twofold in <b>Ir</b><sub><b>2</b></sub><b>L2</b>-treated cells, which correlated with autophagy reticence.</p>\",\"PeriodicalId\":46,\"journal\":{\"name\":\"Journal of Medicinal Chemistry\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":6.8000,\"publicationDate\":\"2024-05-29\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Journal of Medicinal Chemistry\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://pubs.acs.org/doi/10.1021/acs.jmedchem.4c00406\",\"RegionNum\":1,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"CHEMISTRY, MEDICINAL\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Journal of Medicinal Chemistry","FirstCategoryId":"3","ListUrlMain":"https://pubs.acs.org/doi/10.1021/acs.jmedchem.4c00406","RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"CHEMISTRY, MEDICINAL","Score":null,"Total":0}
2-Aryl-1H-imidazo[4,5-f][1,10]phenanthroline-Based Binuclear Ru(II)/Ir(III)/Re(I) Complexes as Mitochondria Targeting Cancer Stem Cell Therapeutic Agents#
A series of novel Ru(II)/Ir(III)/Re(I)-based organometallic complexes [Ru2L1, Ru2L2, Ir2L1, Ir2L2, Re2L1, and Re2L2] have been synthesized to assess their potency and selectivity against multiple cancer cells A549, HCT-116, and HCT-116 colon CSCs. The cytotoxic screening of the synthesized complexes has revealed that complex Ru2L1 and Ir2L2 are two proficient complexes among all, but Ru2L1 is the most potent complex. A significant binding constant value was observed for DNA and BSA in all complexes. Significant lipophilic properties allow them to penetrate cancer cell membranes, and substantial quantum yield (ϕf) values support bioimaging potential. Again, these complexes are particular for mitochondrial localization and produce a profuse amount of ROS to damage the mitochondrial DNA and then G1 phase cell-cycle arrest. Protein expression analysis unveiled that pro-apoptotic Bax protein overexpressed in Ru2L1-treated cells, whereas antiapoptotic Bcl-2 protein was expressed twofold in Ir2L2-treated cells, which correlated with autophagy reticence.
期刊介绍:
The Journal of Medicinal Chemistry is a prestigious biweekly peer-reviewed publication that focuses on the multifaceted field of medicinal chemistry. Since its inception in 1959 as the Journal of Medicinal and Pharmaceutical Chemistry, it has evolved to become a cornerstone in the dissemination of research findings related to the design, synthesis, and development of therapeutic agents.
The Journal of Medicinal Chemistry is recognized for its significant impact in the scientific community, as evidenced by its 2022 impact factor of 7.3. This metric reflects the journal's influence and the importance of its content in shaping the future of drug discovery and development. The journal serves as a vital resource for chemists, pharmacologists, and other researchers interested in the molecular mechanisms of drug action and the optimization of therapeutic compounds.