Synthesis, Anticancer Activity, and Genome Profiling of Thiazolo Arene Ruthenium Complexes

Abstract

Sixteen hydrazinyl-thiazolo arene ruthenium complexes of the general formula [(η(6)-p-cymene)Ru(N,N'-hydrazinyl-thiazolo)Cl]Cl were synthesized. All complexes were tested in vitro for their antiproliferative activity on three tumor cell lines (HeLa, A2780, and A2780cisR) and on a noncancerous cell line (HFL-1). A superior cytotoxic activity of the ruthenium complexes as compared to cisplatin and oxaliplatin, on both cisplatin-sensitive and cisplatin resistant ovarian cancer cells, was observed. In addition, the biological activity of two selected derivatives was evaluated using microarray gene expression assay and ingenuity pathway analysis. p53 signaling was identified as an important pathway modulated by both arene ruthenium compounds. New activated molecules such as FAS, ZMAT3, PRMT2, BBC3/PUMA, and PDCD4, whose overexpressions are correlated with overcoming resistance to cisplatin therapy, were also identified as potential targets. Moreover, the arene ruthenium complexes can be used in association with cisplatin to prevent cisplatin resistance development and synergistically to induce cell death in ovarian cancer cells.

The development of anticancer ruthenium(ii) complexes: from single molecule compounds to nanomaterials

“…designed hydrazinyl-thiazolo arene Ru(II) complexes and these compounds were more cytotoxic to HeLa, A2780 and A2780cisR cells compared to cisplatin and oxaliplatin. 150 The representative complexes, 4l and 4m , were induced HeLa cell death by disrupting mitochondrial membranes and damaging the nucleus. The biological activity of the two compounds was first evaluated using microarray gene expression assay and ingenuity pathway analysis.…”

Study of the cytotoxic and genotoxic potential of the carbonyl ruthenium(II) compound, ct‐[RuCl(CO)(dppb)(bipy)]PF6 [dppb = 1,4‐bis(diphenylphosphino)butane and bipy = 2,2′‐bipyridine], by in vitro and in vivo assays

“…Ruthenium(II) and (III) compounds with different biological ligands have attracted attention in recent years because of their better antitumor activity compared to cisplatin, such as NAMI-A ([ImH]{trans-[RuCl 4 (Im)(DMSO)], Im = imidazole) and KP1019 ([IndH]{trans-[RuCl 4 (Ind) 2 ]}, Ind = indazole), which are in clinical trials, and ruthenium(II) polypyridyl complexes. These compounds have shown low toxicity in healthy tissues in in vitro and in vivo assays (Grozav et al, 2015;Haghdoost et al, 2017;Van Rijt & Sadler, 2009;Wang et al, 2014;Wang, Zhang, Ji, & Chao, 2015). Other anticancer activities include the interaction with proteins, induction of apoptosis, inhibition of metastasis, inhibition of topoisomerase, interaction with DNA and antiangiogenic effects (Bergamo, Masi, Dyson, & Sava, 2008;Du et al, 2011;Li, Wong, Chen, & Zheng, 2012;Martínez, Suárez, Shand, Magliozzo, & Sánchez-Delgado, 2011;Moreno et al, 2011;Nazarov et al, 2013;Sava et al, 2003).…”

Antitumor Activity of a Unique Polymer That Incorporates a Fluorescent Self-Assembled Metallacycle

“…2 Due to the anticancer activity of organometallic ruthenium and platinum complexes, therapeutic SCCs, including these metals as the acceptors, have been prepared in recent years. 3 Different from the clinical drugs, such as cisplatin, imaging capability can also be integrated into these SCC platforms by simply choosing fluorescent ligands as the coordination donors. This subsequently helps to trace the delivery and release of the organometallic drug in vitro and in vivo .…”