G2/M-Phase-Inhibitory Mitochondrial-Depolarizing Re(I)/Ru(II)/Ir(III)-2,2'-Bipyrimidine-Based Heterobimetallic Luminescent Complexes: An Assessment of In Vitro Antiproliferative Activity and Bioimaging for Targeted Therapy toward Human TNBC Cells

Nilmadhab Roy; Shanooja Shanavas; Binoy Kar; Lavanya Thilak Babu; Utpal Das; Seshu Vardhan; Suban K Sahoo; Bipasha Bose; Vijayaraghavan Rajagopalan; Priyankar Paira

doi:10.1021/acsomega.2c08285

G2/M-Phase-Inhibitory Mitochondrial-Depolarizing Re(I)/Ru(II)/Ir(III)-2,2'-Bipyrimidine-Based Heterobimetallic Luminescent Complexes: An Assessment of In Vitro Antiproliferative Activity and Bioimaging for Targeted Therapy toward Human TNBC Cells

ACS Omega. 2023 Mar 21;8(13):12283-12297. doi: 10.1021/acsomega.2c08285. eCollection 2023 Apr 4.

Affiliations

¹ Department of Chemistry, School of Advanced Sciences, Vellore Institute of Technology, Vellore 632014, Tamilnadu, India.
² Department Stem Cells and Regenerative Medicine Centre, Institution Yenepoya Research Centre, Yenepoya University, University Road, Derlakatte, Mangalore 575018, Karnataka, India.
³ Department of Applied Chemistry, S.V. National Institute of Technology (SVNIT), Ichchanath, Surat, Gujarat 395007, India.

Abstract

Triple-negative breast cancer (TNBC) is an extremely vicious subtype of human breast cancer having the worst prognosis along with strong invasive and metastatic competency. Hence, it can easily invade into blood vessels, and presently, no targeted therapeutic approach is available to annihilate this type of cancer. Metal complexes have successfully stepped into the anticancer research and are now being applauded due to their anticancer potency after the discovery of cisplatin. Many of these metal complexes are also well recognized for their activity toward breast cancer. As the TNBC is a very dangerous subtype and has long been a challenging ailment to treat, we have intended to develop a few brand new mixed metallic Ru(II)/Ir(III)/Re(I)-2,2'-bipyrimidine complexes [L'Re2], [L'RuRe], and [L'IrRe] to abate the unbridled proliferation of TNBC cells. The potency of the complexes against TNBC cells has been justified using MDA-MB-468 TNBC cell lines where complex [L'IrRe] has displayed significant potency among all the three complexes with an IC₅₀ value of 24.12 μM. The complex [L'IrRe] has been competent to cause apoptosis of TNBC cells through inhibition of the G2/M phase in the cell cycle in association with a profuse amount of ROS generation and mitochondrial depolarization.