Antitumor activity of iridium/ruthenium complexes containing Nitro -substituted quinoline ligands in vivo and in vitro

Recruitment of hexahydroquinoline as anticancer scaffold targeting inhibition of wild and mutants EGFR (EGFR WT , EGFR T790M , and EGFR L858R )

“…The most important mechanism chemotherapeutics eradicate cancer cells is apoptosis induction 78 , 79 . Cellular alterations brought on by apoptosis include the translocation of phosphatidylserine (PS) from the inside to the outside via the plasma membrane 80 , 81 .…”

A Λ-Ir(iii)-phenylquinazolinone complex enhances ferroptosis by selectively inhibiting metallothionein-1

“…When compared to the rst reported Iridium(III)-based ferroptosis inducer (IrFN), 19 L-IrPPQ also displayed higher cytotoxicity toward PANC-1 cells than IrFN (Table S2 †). In addition, the photocytotoxicity index of L-IrPPQ was higher than most reported ferroptosis-inducing metal agents (Table S2 †), [20][21][22][23][24][25][26][32][33][34][35] conrming the high cancer cell killing efficiency as a potential PDT agent.…”

“…16,17 In particular, for pancreatic ductal adenocarcinoma (PDAC), a ferroptosis-sensitive cell line, deletion of Slc7a11 by ferroptosis inducers resulted in excellent inhibition of PDAC in mice. 18 Recently, the development of metal complexes (Ir(III), [19][20][21][22][23][24][25][26] Fe(III), [27][28][29][30][31] and Ga(III) [32][33][34] ) by inducing ferroptosis has shown signicant advantages in disrupting Fe metabolism, glutathione metabolism and regulating immune responses. In addition, targeting ferroptosis suppressor protein-1 (FSP1, a glutathione-independent ferroptosis suppressor) by an AIE-based Pt(II) complex induced ferroptosis with potential to overcome drug resistance.…”

Cellular Mechanistic Considerations on Cytotoxic Mode of Action of Phosphino Ru(II) and Ir(III) Complexes

“…The consequence of this is the aforementioned process of apoptosis. [16,17,21,25] In particular, the half-sandwich iridium(III) complexes show potential antiproliferative activity, and the ability to (i) inhibit the migration of cancer cells, (ii) accumulate in mitochondria, (iii) reduce the mitochondrial membrane potential, and (iv) increase the level of intracellular reactive oxygen species. [16,17,23,[26][27][28] While, the ruthenium complexes affect not only mitochondria but also enzymes such as carbonic anhydrase, and topoisomerase I, which are upregulated in cancer cells.…”

“…Furthermore, these complexes have the ability to accumulate in intracellular lysosomes leading to their damage. The consequence of this is the aforementioned process of apoptosis [16,17,21,25] …”