Assessment of antiproliferative activity of new half‐sandwich arene Ru (II) furylbenzhydrazone complexes

Abstract

The study attempts in finding an effective anticancer activity of six new arene ruthenium (II) complexes possessing the composition of [(η 6 -arene)Ru(L)Cl] (arene = benzene (1-3) /p-cymene (4-6); L = 2-furyl methyl benzhydrazones).Elemental analysis, Fourier transform infrared spectroscopy (FT-IR), UV-vis, nuclear magnetic resonance (NMR), and high resolution mass spectrometry (HR-MS) techniques were utilized to study the synthesized complexes. The single crystal X-ray crystallography validated the bidentate mode of coordination of the benzhydrazone ligand and pseudo-octahedral geometry around ruthenium ion. MTT assay has been performed to assess the in vitro growth of cancer cell inhibition ability of all the complexes against MCF-7(breast carcinoma), HuH-7 (hepatocellular carcinoma), and HeLa (cervical cancer), along with non-cancerous L132 (human lung epithelium) cell lines. It has been found that all the six complexes exhibit good to excellent cytotoxicity toward the cancer cell lines tested with low IC 50 values compared to cisplatin. Among the synthesized complexes, complex 6 shows potential cytotoxicity against all the cancer cell lines. The observed higher cytotoxicity of the complex 6 may be due to the electron donating methoxy group of the ligand and hydrophobic character of arene moiety. Eventually, the staining techniques such as AO-EB, HOECHST 33342, RH-123, and reactive oxygen species (ROS) establish that all the complexes bring about cell death via apoptosis. The present research results emphasize the more possibility to promote potential arene ruthenium anticancer agents.

Exploration of Antiproliferative Activity and Apoptosis Induction of New Nickel(II) Complexes Encompassing Carbazole Ligands

“…This is due to the structural changes (chromosomal condensation and nuclear fragmentation) that happened attributed to apoptosis. 31 ROS Detection. ROS, like hydrogen peroxide, superoxide anion, and hydroxyl radical, are produced on mitochondrial oxidative metabolism along with cell's reaction toward cytokines and bacterial invasion.…”

“…Bright blue fluorescence patches were observed for the complex treated cells after 24 h (Figure B). This is due to the structural changes (chromosomal condensation and nuclear fragmentation) that happened attributed to apoptosis …”

“…This is due to the structural changes (chromosomal condensation and nuclear fragmentation) that happened attributed to apoptosis. 31 …”

Studies on anticancer properties with varying co-ligands in a Ru(ii) arene benzimidazole system

“…7,8 Among the explored Ru-based metallodrugs, imidazolium trans-[tetrachloro (dimethyl sulfoxide)(imidazole)ruthenium(III)] and indazolium trans-[tetrachlorobis(1H-indazole)ruthenium(III)], which are abbreviated as NAMI-A and KP1019, respectively, entered clinical trials, but the studies were put to rest due to transient nephrotoxicity caused by NAMI-A and poor solubility of KP1019 in water. 9,10 However two other complexes, [Ru(η 6 -p-cymene)Cl 2 (1,3,5-triaza-7-phosphaadamantane)] or RAPTA-C, and KP1339 which is the sodium salt of KP1019 are currently undergoing clinical trials. 11,12 Half sandwich arene ruthenium(II) complexes [(η 6 -arene)Ru (X)(Y)(Z)], in particular, have attracted attention as promising candidates for anticancer activities.…”

“…9,10 However two other complexes, [Ru(η 6 -p-cymene)Cl 2 (1,3,5-triaza-7-phosphaadamantane)] or RAPTA-C, and KP1339 which is the sodium salt of KP1019 are currently undergoing clinical trials. 11,12 Half sandwich arene ruthenium(II) complexes [(η 6 -arene)Ru (X)(Y)(Z)], in particular, have attracted attention as promising candidates for anticancer activities. 13,14 They are a class of compounds having a piano stool geometry (Fig.…”