Iridium(iii)–Cp*-(imidazo[4, 5-f][1, 10]phenanthrolin-2-yl)phenol analogues as hypoxia active, GSH-resistant cancer cytoselective and mitochondria-targeting cancer stem cell therapeutic agents. Issue 14 (16th March 2022)

• Record Type: Journal Article
• Authors: Kar, Binoy; Shanavas, Shanooja; Nagendra, Apoorva H.; Das, Utpal; Roy, Nilmadhab; Pete, Sudhindra; Sharma S, Ajay; De, Sourav; Kumar S K, Ashok; Vardhan, Seshu; Sahoo, Suban K.; Panda, Debashis; Shenoy, Sudheer; Bose, Bipasha; Paira, Priyankar
• Is Part Of: Dalton transactions. Volume 51:Issue 14(2022)
• Page Start: 5494
• Page End: 5514
• Publication Date: 2022-03-16
• Subjects: Chemistry, Inorganic -- Periodicals; Chemistry, Physical and theoretical -- Periodicals; Chemistry, Inorganic -- Periodicals; 546.05
• DOI: 10.1039/d2dt00168c
• Languages: English
• ISSNs: 1477-9226

Abstract

Abstract : GSH-resistant, hypoxia active iridium(iii )–Cp*-(imidazo[4, 5- f ][1, 10]phenanthrolin-2-yl)phenol complexes were developed as highly cytoselective anticancer agents and mitochondria-targeting CSC therapeutic agents. Abstract : Herein, we have introduced a series of iridium(iii )–Cp*-(imidazo[4, 5- f ][1, 10]phenanthrolin-2-yl)phenol complexes via a convenient synthetic methodology, which act as hypoxia active and glutathione-resistant anticancer metallotherapeutics. The [Ir III (Cp*)(L5)(Cl)](PF6 ) (IrL5 ) complex exhibited the best cytoselectivity, GSH resistance and hypoxia effectivity in HeLa and Caco-2 cells among the synthesized complexes. IrL5 also exhibited highly cytotoxic effects on the HCT-116 CSC cell line. This complex was localized in the mitochondria and subsequent mitochondrial dysfunction was observed via MMP alteration and ROS generation on colorectal cancer stem cells. Cell cycle analysis also established the potential of this complex in mediating G2/M phase cell cycle arrest.