3 research outputs found
New tailored substituted benzothiazole Schiff base Cu(II)/Zn(II) antitumor drug entities: effect of substituents on DNA binding profile, antimicrobial and cytotoxic activity
<p>New tailored Cu(II) & Zn(II) metal-based antitumor drug entities were synthesized from substituted benzothiazole <i>o</i>‒vanillin Schiff base ligands. The complexes were thoroughly characterized by elemental analysis, spectroscopic studies {IR, <sup>1</sup>H & <sup>13</sup>C NMR, ESI−MS, EPR} and magnetic susceptibility measurements. The structure activity relationship (SAR) studies of benzothiazole Cu(II) & Zn(II) complexes having molecular formulas [C<sub>30</sub>H<sub>22</sub>CuN<sub>5</sub>O<sub>7</sub>S<sub>2</sub>], [C<sub>30</sub>H<sub>20</sub>Cl<sub>2</sub>CuN<sub>5</sub>O<sub>7</sub>S<sub>2</sub>], [C<sub>30</sub>H<sub>20</sub>CuF<sub>2</sub>N<sub>5</sub>O<sub>7</sub>S<sub>2</sub>], [C<sub>30</sub>H<sub>22</sub>N<sub>4</sub>O<sub>4</sub>S<sub>2</sub>Zn], [C<sub>30</sub>H<sub>20</sub>Cl<sub>2</sub>N<sub>4</sub>O<sub>4</sub>S<sub>2</sub>Zn], and [C<sub>30</sub>H<sub>20</sub>F<sub>2</sub>N<sub>5</sub>O<sub>7</sub>S<sub>2</sub>Zn], with CT‒DNA were performed by employing absorption, emission titrations, and hydrodynamic measurements. The DNA binding affinity was quantified by <i>K</i>
<sub>b</sub> and <i>K</i>
<sub>sv</sub> values which gave higher binding propensity for chloro-substituted Cu(II) [C<sub>30</sub>H<sub>20</sub>Cl<sub>2</sub>CuN<sub>5</sub>O<sub>7</sub>S<sub>2</sub>] complex, suggestive of groove binding mode with subtle partial intercalation. Molecular properties and drug likeness profile were assessed for the ligands and all the Lipinski’s rules were found to be obeyed. The antimicrobial potential of ligands and their Cu(II) & Zn(II) complexes were screened against some notably important pathogens <i>viz</i>., <i>E. coli, S. aureus, P. aeruginosa, B. subtilis</i>, and <i>C. albicans</i>. The cytotoxicity of the complexes [C<sub>30</sub>H<sub>20</sub>Cl<sub>2</sub>CuN<sub>5</sub>O<sub>7</sub>S<sub>2</sub>], [C<sub>30</sub>H<sub>20</sub>CuF<sub>2</sub>N<sub>5</sub>O<sub>7</sub>S<sub>2</sub>], [C<sub>30</sub>H<sub>20</sub>Cl<sub>2</sub>N<sub>4</sub>O<sub>4</sub>S<sub>2</sub>Zn], and [C<sub>30</sub>H<sub>20</sub>F<sub>2</sub>N<sub>5</sub>O<sub>7</sub>S<sub>2</sub>Zn] were evaluated against five human cancer cell lines <i>viz</i>., MCF‒7 (breast), MIA‒PA‒CA‒2 (pancreatic), HeLa (cervix) and Hep‒G2 (Hepatoma) and A498 (Kidney) by SRB assay which revealed that chloro-substituted [C<sub>30</sub>H<sub>20</sub>Cl<sub>2</sub>CuN<sub>5</sub>O<sub>7</sub>S<sub>2</sub>] complex, exhibited pronounced specific cytotoxicity with GI<sub>50</sub> value of 4.8 μg/ml against HeLa cell line. Molecular docking studies were also performed to explore the binding modes and orientation of the complexes in the DNA helix.</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