Synthesis, cytotoxicity and docking studies (with SARS-CoV-2) of water-soluble binuclear Ru- p-cymene complex holding indole thiosemicarbazone ligand

Jebiti Haribabu; Nithya Balakrishnan; Srividya Swaminathan; Jerome Peter; Dasararaju Gayathri; Cesar Echeverria; Nattamai Bhuvanesh; Ramasamy Karvembu

doi:10.1016/j.inoche.2021.109029

Synthesis, cytotoxicity and docking studies (with SARS-CoV-2) of water-soluble binuclear Ru- p-cymene complex holding indole thiosemicarbazone ligand

Inorg Chem Commun. 2021 Dec:134:109029. doi: 10.1016/j.inoche.2021.109029. Epub 2021 Oct 28.

Authors

Jebiti Haribabu^{1

2}, Nithya Balakrishnan¹, Srividya Swaminathan¹, Jerome Peter^{1

3}, Dasararaju Gayathri⁴, Cesar Echeverria², Nattamai Bhuvanesh⁵, Ramasamy Karvembu¹

Affiliations

¹ Department of Chemistry, National Institute of Technology, Tiruchirappalli 620015, India.
² Facultad de Medicina, Universidad de Atacama, Copayapu 485, 1531772 Copiapo, Chile.
³ Division of Materials Science and Chemical Engineering (MSE), Hanyang University (ERICA), Ansan, Republic of Korea - 15588.
⁴ Centre of Advanced Study in Crystallography and Biophysics, University of Madras, Guindy Campus, Chennai 600025, India.
⁵ Department of Chemistry, Texas A & M University, College Station, TX 77842, USA.

Abstract

A water-soluble binuclear organometallic Ru-p-cymene complex [Ru(η⁶-p-cymene)(η²-L)]₂ (1) was prepared from (E)-2-((1H-indol-3-yl)methylene)-N-phenylhydrazine-1-carbothioamide (HL) and [RuCl₂(p-cymene)]₂ in methanol at room temperature under inert atmosphere. The structure of binuclear complex was analyzed by UV-Visible, FT-IR, NMR and mass spectroscopic methods. The solid-state structure of the complex was ascertained by single crystal X-ray diffraction technique. The complex exhibited pseudo-octahedral (piano-stool) geometry around Ru(II) ion. The cytotoxic property of the ligand and complex along with cisplatin was investigated against A549-lung, MCF-7-breast, HeLa-cervical, HepG-2-liver, T24-urinary bladder and EA.hy926-endothelial cancer cells, and Vero-kidney epithelial normal cells. The complex exhibited superior activity than cisplatin against A549, HeLa and T24 cancer cells with the IC₅₀ values of 7.70, 11.2, and 5.05 µM, respectively. The complexes were cytotoxic specifically to the cancer cells. Molecular docking studies showed good binding potential of the ligand and complex with the spike protein and main protease of SARS-CoV-2, indicating the promising role of these compounds as antiviral compounds.

Keywords: Cytotoxicity; Molecular docking; Piano-stool; Ru(II)-arene complex; SARS-CoV-2; Thiosemicarbazone.