Organometallic (η⁶‐p‐cymene)ruthenium(II) complexes with thiazolyl‐based organic twigs: En route towards targeted delivery via human serum albumin of the potential anticancer agents

Abstract

In this article, we have designed the new ruthenium(II) p‐cymene complexes [Ru(η6‐p‐cymene) HLThz,Me Cl] 1 and [Ru(η6‐p‐cymene) HLThz Cl] 2 with two auxiliary ligand (E)‐1‐(((5‐methylthiazol‐2‐yl)imino)methyl)naphthalen‐2‐ol (HLThz,Me) and (E)‐1‐((thiazol‐2‐ylimino)methyl)naphthalen‐2‐ol (HLThz), keeping in mind the vehicle HSA. The spectroscopic techniques, namely, Fourier transform infrared spectroscopy (FT‐IR), proton nuclear magnetic resonance (1H NMR), 13C NMR, and elemental analysis were employed for the characterization. The single X‐ray crystallography ascertains the molecular structure of the representative complex [Ru(η6‐p‐cymene) HLThz,Me Cl] 1. Furthermore, the density functional theory (DFT) calculation was performed for geometry optimization and frontier molecular orbitals analysis. Moreover, in silico studies were carried out to understand the binding site and the mode of interaction of the complexes with human serum albumin (HSA). The in vitro interaction of the HSA measured extrinsic fluorescence at various temperatures, namely, 298, 303, and 308 K, whereas the intrinsic fluorescence extent was evaluated in the presence of 8‐anilinonaphthalene‐1‐sulfonic acid (ANS). The cytotoxicity of these compounds was evaluated against HeLa, MCF7, HepG2, A549, and A2780 cancer cells and compared with HEK293 non‐tumorigenic cells (cisplatin and RAPTA‐C as control). The complex 1 showed significantly good cytotoxicity in the range of IC50 value <10 μM against A2780 (ovarian cancer) and HepG2 (liver) cells and lower toxicity up to >100 μM. These findings give illustrative insight into the binding propensity of complexes 1 and 2 with HSA (model protein). Further, they can be explored for en route drug delivery to a specific site as anticancer metallodrugs.

Aminobenzimidazole‐based (η6‐p‐cymene)ruthenium (II) complexes as nascent anticancer chemotherapeutics: Synthesis, crystal structure, DFT studies, HSA interactions, molecular docking, and cytotoxicity

“…Some examples are as follows: Yellol et al [26] have reported the ruthenium arenes complexes of benzimidazole-derived derivatives and studies their cytotoxic potential compared with cisplatin (standard drug); Stepanenko et al [43] reported 3-(1H-benzimidazol-2-yl)-1H-pyrazolo [3,4-b]pyridines derived ruthenium complexes as potential anticancer agents; and Martínez-Alonso et al [44] also reported aryldiazole ruthenium complexes and studied their anticancer properties. In recent years, we have reported several Ru-based organometallic complexes with favorable antitumor properties, [38][39][40][41][42] and we are still striving to develop new Ru-based organometallic compounds that can exhibit better therapeutic efficacy.…”

“…[32] Literature review suggests that benzimidazole-based platinum complexes and their cytotoxicity have been studied extensively to develop new antitumor drugs. [36][37][38][39][40][41][42] On the contrary, studies on the non-platinum-based benzimidazole-derived metal complexes, particularly organometallic compounds, are less explored. Some examples are as follows: Yellol et al [26] have reported the ruthenium arenes complexes of benzimidazole-derived derivatives and studies their cytotoxic potential compared with cisplatin (standard drug); Stepanenko et al [43] reported 3-(1H-benzimidazol-2-yl)-1H-pyrazolo [3,4-b]pyridines derived ruthenium complexes as potential anticancer agents; and Martínez-Alonso et al [44] also reported aryldiazole ruthenium complexes and studied their anticancer properties.…”