GSH resistant, luminescent 2-(pyren-1-yl)-1H-imidazo[4,5-f][1,10]phenanthroline-based Ru(ii)/Ir(iii)/Re(i) complexes for phototoxicity in triple-negative breast cancer cells

Abstract

Selective chemotherapeutic strategies necessitate the emergence of a photosensitive scaffold to abate the nuisance of cancer. In the current context, photo-activated chemotherapy (PACT) has, therefore, appeared to be very effective to vanquish the vehemence of triple-negative breast cancer (TNBC). Metal complexes have been identified to act well against cancer cell microenvironment (high GSH content, low pH, and hypoxia), and thus they have been employed in the treatment of various types of cancer. As TNBC is very challenging to treat owing to its poor prognosis, lack of a specific target, high chance of relapse, and strong metastatic ability, herein we have aspired to design GSH-resistant phototoxic Ru(II)/Ir(III)/Re(I) based pyrene imidazophenathroline complexes to selectively avert the triple-negative breast cancer. The application of complexes, [RuL], [IrL], and [ReL] in the absence and in the presence of GSH against MDA-MB-231TNBC cells, has revealed that they are very active upon irradiation of visible light compared to dark due to the creation of copious singlet oxygen (¹O₂) as reactive oxygen species (ROS). Among three synthesized complexes, [IrL] has shown outstanding potency (IC₅₀ = 3.70 in the absence of GSH and IC₅₀ = 3.90 in the presence of GSH). Also, the complex, [IrL] is capable of interacting with DNA with the highest binding constant (K_b = 0.023 × 10⁶ M⁻¹) along with higher protein binding affinity (K_BSA = 0.0321 × 10⁶ M⁻¹). Here, it has been unveiled that all the complexes have been entitled to involve DNA covalent interaction through the available sites of both adenine and guanine bases.