3 research outputs found
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<sup>II</sup>–Sn<sup>IV</sup> (<b>1</b>) and Ni<sup>II</sup>–Sn<sup>IV</sup> (<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 (GI<sub>50</sub> 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 (η<sup>6</sup>‑Arene)ruthenium–Organotin Complex as an Efficient Topoisomerase Iα Inhibitor
The chloro-bridged heterobimetallic
complex (η<sup>6</sup>-hexamethylbenzene)ÂRuÂ(dmp)Â(μ-Cl)<sub>2</sub>SnÂ(CH<sub>3</sub>)<sub>2</sub>Cl<sub>2</sub> was designed,
synthesized, and characterized
by various spectroscopic methods, viz. IR, <sup>1</sup>H and <sup>13</sup>C 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 (η<sup>6</sup>‑Arene)ruthenium–Organotin Complex as an Efficient Topoisomerase Iα Inhibitor
The chloro-bridged heterobimetallic
complex (η<sup>6</sup>-hexamethylbenzene)ÂRuÂ(dmp)Â(μ-Cl)<sub>2</sub>SnÂ(CH<sub>3</sub>)<sub>2</sub>Cl<sub>2</sub> was designed,
synthesized, and characterized
by various spectroscopic methods, viz. IR, <sup>1</sup>H and <sup>13</sup>C 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