Organometallic Anticancer Compounds: Novel Half-Sandwich Ru(II)- and Co(II)-Arene Complexes, Their Cytotoxicity, and Apo
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rganometallic Anticancer Compounds: Novel Half-Sandwich Ru(II)- and Co(II)-Arene Complexes, Their Cytotoxicity, and Apoptosis-Inducing Activity in Liver Cancer Cells P. Shridhara, S. Purushothamana, and M. Ganeshpandiana,* a Department
of Chemistry, SRM Institute of Science & Technology, Potheri, Kattankulathur Chengalpattu District, Tamil Nadu, 603203 India *e-mail: [email protected] Received August 26, 2020; revised October 15, 2020; accepted October 29, 2020
Abstract—Organometallic complexes in many instances are characterised by potential anti-proliferative activity against different types of cancer cells. In particular, half-sandwich Ru(II)–arene and Co(II)-arene complexes exhibit in vitro and in vivo anticancer activity. Here we report synthesis of two organometallic half-sandwich complexes containing diimine ligand, [Ru(η6-p-cymene)(BIAN)Cl](PF6) and [Co(η5-C5Me5)(BIAN)CO](ClO4)2, where η5-C5Me5 is pentmethylcyclopentadiene and BIAN is bis(4-tert-butylphenylimino)acenaphthene. According to gel electrophoresis data, Co(II)-arene complex exhibits higher DNA cleavage activity than Ru(II)-arene complex due to size and charge of complex cation, and both complexes demonstrate maximum degradation of DNA upon activation by UVA light. In vitro cytotoxicity tests of complexes against human lung carcinoma (A549) and human ovarian carcinoma (A2780) cells indicate cytotoxicity of complexes comparable with cis-platin. The morphological studies have revealed that Co-arene complex induces both apoptotic and necrotic cells death. Keywords: organometallic anticancer agents, Ru-arene complex, Co-arene complex, DNA cleavage, cytotoxicity, apoptosis
DOI: 10.1134/S1070363220110249 INTRODUCTION A studied in depth and used on a broad scale anticancer organic platinum drug cisplatin is effective towards some types of cancer but exhibits a number of side effects like kidney damage (nephrotoxicity), hear loss (ototoxicity), nausea, and vomiting that make its dosage administered to patients very limited. For this reason, nowadays, the study of other organometallic compounds with lower side effects is a hot point for organic and medicinal chemists [1–4]. Nowadays, some ruthenium complexes are the building blocks of metal-based anticancer drugs and those act as potential antimetastatic agents [5–9]. The Ru-based anticancer products such as imidazolium trans-[tetrachlorido(dimethylsulfoxide)(1H-imidazole)ruthenate(III)] (NAMI-A) and sodium salt of indazolium trans[tetrachloridobis(1H-indazole)ruthenate(III)] (KP1339) are currently under phase II clinical trials [10, 11]. Cobalt complexes also play a significant role in anticancer drug development because cobalt compounds are considered to be less toxic than those of platinum [12]. Therefore the biocompatible ruthenium and cobalt complexes, that
possess several favourable physico-chemical features, could be favourable in design of non-platinum anticancer agents with less side effects [13]. Sadler and co-workers determined that Ru-arene complexes exhibited efficient anticancer activi
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