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Synthesis and Structure of Arene Ru(II) NO‑Chelating Complexes: In Vitro Cytotoxicity and Cancer Cell Death Mechanism

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journal contribution
posted on 08.04.2020, 20:29 authored by Sundarraman Balaji, Mohamed Kasim Mohamed Subarkhan, Rengan Ramesh, Hangxiang Wang, David Semeril
A panel of six new structurally related organometallic arene Ru­(II) complexes of general composition [(η6-benzene)­Ru­(L)­Cl] (13) and [(η6-p-cymene)­Ru­(L)­Cl] (46) (L = dimethylaminobenzhydrazones) have been designed and synthesized in search of new ruthenium anticancer drugs. The identities of the synthesized complexes have been well-established by elemental analysis and various spectral (FT-IR, UV–vis, NMR, and HR-MS) methods. The solid-state molecular structures of the ruthenium complexes were determined with the help of X-ray crystallography and confirms the presence of a pseudo-octahedral geometry around ruthenium. Furthermore, cytotoxicity of the complexes has been unveiled with the aid of MTT assay against A549 (lung carcinoma), LoVo (colon adenocarcinoma), HuH-7 (hepato cellular carcinoma) along with the noncancerous 16HBE (human lung bronchial epithelium) cells and compared with the effect of the standard drug cisplatin. Interestingly, complexes 4, 5, and 6 which contain a p-cymene moiety induce a remarkable decrease of cell viability against all the cancer cells tested. The capacity corresponding to the inhibition of A549 cells proliferation was analyzed by 5-ethynyl-2-deoxyuridine (EdU) incorporation assay and indicated a notable effect of p-cymene counterparts 4, 5, and 6 over cisplatin. Further studies such as AO-EB (acridine orange–ethidium bromide) staining, flow cytometry, and Western blot analyses on cell death mechanism signified that the cytotoxicity was associated with apoptosis in cancer cells. This clearly suggests that p-cymene-capped Ru­(II) complexes are also one of the propitious cancer therapeutic candidates and are worthy of further investigations.