Design, Synthesis, DNA/HSA Binding, and Cytotoxic Activity of Half-Sandwich Ru(II)-Arene Complexes Containing Triarylamine-Thiosemicarbazone Hybrids

Mathiyan Muralisankar; Ramachandran Dheepika; Jebiti Haribabu; Chandrasekar Balachandran; Shin Aoki; Nattamai S P Bhuvanesh; Samuthira Nagarajan

doi:10.1021/acsomega.9b01022

Design, Synthesis, DNA/HSA Binding, and Cytotoxic Activity of Half-Sandwich Ru(II)-Arene Complexes Containing Triarylamine-Thiosemicarbazone Hybrids

ACS Omega. 2019 Jul 5;4(7):11712-11723. doi: 10.1021/acsomega.9b01022. eCollection 2019 Jul 31.

Authors

Mathiyan Muralisankar¹, Ramachandran Dheepika¹, Jebiti Haribabu^{2

3}, Chandrasekar Balachandran³, Shin Aoki^{3

3}, Nattamai S P Bhuvanesh⁴, Samuthira Nagarajan¹

Affiliations

¹ Department of Chemistry, Central University of Tamil Nadu, Thiruvarur 610005, India.
² Department of Chemistry, National Institute of Technology, Tiruchirappalli 620015, India.
³ Faculty of Pharmaceutical Sciences and Research Institute of Science and Technology, Tokyo University of Science, 2641 Yamazaki, Noda 278-8510, Japan.
⁴ Department of Chemistry, Texas A & M University, College Station, Texas 77842, United States.

Abstract

Organoruthenium complexes are potent alternatives for platinum-based complexes because of their superior anticancer activity. In this investigation, a series of new Ru(II)-arene complexes with triarylamine-thiosemicarbazone hybrid ligands with higher anticancer activity than cisplatin are reported. The molecular structure of the ligands and complexes was confirmed spectroscopically and supported by single-crystal X-ray crystallography. These complexes adopted a three-leg piano stool geometry. All the Ru(II)-arene complexes were systematically investigated for their in vitro cytotoxicity against human cervical (HeLa S3), lung (A549) cancer, and human normal lung (IMR-90) cell lines using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. Interestingly, a pyrrolidine-attached Ru(II)-benzene complex exhibited superior activity against cancer cells with low IC₅₀ values, and colony formation study showed complete inhibition at 5 and 10 μM concentration. Furthermore, morphological changes assessed by acridine orange and propidium iodide staining revealed that the cell death occurred by apoptosis. In addition, the interaction between synthesized Ru(II)-arene complexes and DNA/protein was explored by absorption and emission spectroscopy methods. These synthesized new organoruthenium complexes can be used for developing new metal-based anticancer drugs.