Carbohydrate-based heteronuclear complexes as topoisomerase Iα inhibitor: approach toward anticancer chemotherapeutics

<p>Due to the critical role of cellular enzymes necessary for cell proliferation by deciphering topological hurdles in the process of DNA replication, topoisomerases have been one of the major targets in the anticancer drug development area. A need, therefore, arises for new metallodrugs that specifically recognizes DNA and inhibits the activity of topoisomerase enzymes, herein, we report the synthesis and characterization of new metal-based glycoconjugate entities containing heterobimetallic core Cu^II–Sn^IV (<b>1</b>) and Ni^II–Sn^IV (<b>2</b>) derived from N-glycoside ligand (<b>L</b>). The optimized structure of complex <b>1</b> and other significant vibrational modes have been explained using dispersion corrected B3LYP/DFT calculations. <i>In vitro</i> DNA binding profile of the <b>L</b> and both the complexes <b>1</b> and <b>2</b> were done by various biophysical studies. Complex <b>1</b> breaks pBR322 DNA <i>via a</i> hydrolytic means which was validated by T4 DNA enzymatic assay. To get a mechanistic insight of mode of action topoisomerase I (Topo I) inhibition assay was carried out. Also, we have taken the help of molecular modeling studies in accordance with experimental findings. <i>In vitro</i> cytotoxicity of the complex <b>1</b> was evaluated against a panel of cancer cells which exhibited remarkably good anticancer activity (GI₅₀ values <10 μg/ml). Moreover, intracellular localization of the complex <b>1</b> was visualized by confocal microscopy against HeLa cells.</p

A Chloro-Bridged Heterobimetallic (η⁶‑Arene)ruthenium–Organotin Complex as an Efficient Topoisomerase Iα Inhibitor

The chloro-bridged heterobimetallic complex (η⁶-hexamethylbenzene)­Ru­(dmp)­(μ-Cl)₂Sn­(CH₃)₂Cl₂ was designed, synthesized, and characterized by various spectroscopic methods, viz. IR, ¹H and ¹³C NMR, and ESI MS, and single-crystal X-ray crystallography as an approach toward multitargeting metal-based potential anticancer drug candidates. In vitro DNA binding studies confirmed the binding affinity of the complex toward the minor groove of DNA, which is further validated by docking studies. Furthermore, the complex exhibited significant inhibitory effects on topoisomerase Iα at a very low concentration (∼8 μM). The cytotoxicity of the complex against HeLa and HepG2 cancer cell lines was evaluated, which revealed significant regression in cancerous cells in comparison with the standard drug

A Chloro-Bridged Heterobimetallic (η⁶‑Arene)ruthenium–Organotin Complex as an Efficient Topoisomerase Iα Inhibitor

The chloro-bridged heterobimetallic complex (η⁶-hexamethylbenzene)­Ru­(dmp)­(μ-Cl)₂Sn­(CH₃)₂Cl₂ was designed, synthesized, and characterized by various spectroscopic methods, viz. IR, ¹H and ¹³C NMR, and ESI MS, and single-crystal X-ray crystallography as an approach toward multitargeting metal-based potential anticancer drug candidates. In vitro DNA binding studies confirmed the binding affinity of the complex toward the minor groove of DNA, which is further validated by docking studies. Furthermore, the complex exhibited significant inhibitory effects on topoisomerase Iα at a very low concentration (∼8 μM). The cytotoxicity of the complex against HeLa and HepG2 cancer cell lines was evaluated, which revealed significant regression in cancerous cells in comparison with the standard drug