7 research outputs found
Synthesis, CP-MAS NMR Characterization, and Antibacterial Activities of Glycine and Histidine Complexes of Cd(SeCN) 2
The synthesis and characterization of cadmium and mercury complexes of selenocyanate of the type [(L)M(SeCN)2] are described, where L is L-Histidine (His) or L-Glycine (Gly) and M is Cd2+ or Hg2+. These complexes are obtained by the reaction of 1 equivalent of respective amino acids with metal diselenocyanate precursor in a mixture of solvents (methanol : water = 1 : 1). These synthesized compounds are characterized by analytical and various spectroscopic techniques such as elemental analysis (EA), IR, H,1 and C13 NMR in solution and in the solid state for C13 and N15. The in vitro antibacterial activities of these complexes have been investigated with standard type cultures of Escherichia coli (MTCC 443), Klebsiella pneumoniae (MTCC 109), Pseudomonas aeruginosa (MTCC 1688), Salmonella typhi (MTCC 733), and Staphylococcus aureus (MTCC 737)
New bipyridine gold(III) dithiocarbamate-containing complexes exerted a potent anticancer activity against cisplatin-resistant cancer cells independent of p53 status
We synthesized, characterized and tested in a panel of cancer cell lines, nine new bipyridine gold(III) dithiocarbamate-containing complexes. In vitro studies demonstrated that compounds 1, 2, 4, 5, 7 and 8 were the most cytotoxic in prostate, breast, ovarian cancer cell lines and in Hodgkin lymphoma cells with IC50 values lower than the reference drug cisplatin. The most active compound 1 was more active than cisplatin in ovarian (A2780cis and 2780CP-16) and breast cancer cisplatin-resistant cells. Compound 1 determined an alteration of the cellular redox homeostasis leading to increased ROS levels, a decrease in the mitochondrial membrane potential, cytochrome-c release from the mitochondria and activation of caspases 9 and 3. The ROS scavenger NAC suppressed ROS generation and rescued cells from damage. Compound 1 resulted more active in tumor cells than in normal human Mesenchymal stromal cells. Gold compounds were active independent of p53 status: exerted cytotoxic effects on a panel of non-small cell lung cancer cell lines with different p53 status and in the ovarian A2780 model where the p53 was knocked out. In conclusion, these promising results strongly indicate the need for further preclinical evaluation to test the clinical potential of these new gold(III) complexes
Tetrakis(thione)platinum(II) complexes: synthesis, spectroscopic characterization, crystal structures, and <i>in vitro</i> cytotoxicity
<div><p>A new series of platinum(II) complexes based on thione ligands with general formula [Pt(thione)<sub>4</sub>]X<sub>2</sub> (X<sup>−</sup> = Cl<sup>−</sup>, NO<sub>3</sub><sup>−</sup>) has been synthesized and characterized using CHNS elemental analysis, infrared, <sup>1</sup>H and <sup>13</sup>C solution-state NMR as well as <sup>13</sup>C and <sup>15</sup>N solid-state NMR spectroscopy, and X-ray crystallography. The spectroscopic methods confirm the coordination of Pt(II) with thiocarbonyl groups via sulfur of the thione ligands. The X-ray structures showed a distorted square planar geometry for <b>1</b>, [Pt(MeImt)<sub>4</sub>]Cl<sub>2</sub> (MeImt = N-Methylimidazolidine-2-thione) while the hydrogen bonding interactions in <b>7</b>, [Pt(<i>i</i>PrImt)<sub>4</sub>](NO<sub>3</sub>)<sub>2</sub>·0.6(H<sub>2</sub>O) induce a bent see-saw distortion relative to the ideal square planar geometry. The <i>in vitro</i> cytotoxicity studies showed that <b>2</b>, [Pt(EtImt)<sub>4</sub>]Cl<sub>2</sub> is generally the most effective, a two-fold better cytotoxic agent than cisplatin and carboplatin against MCF7 (human breast cancer).</p></div
Impedance technology reveals correlations between cytotoxicity and lipophilicity of mono and bimetallic phosphine complexes
Label free impedance technology enables
the monitoring of cell response patterns post treatment
with drugs or other chemicals. Using this technology,
a correlation between the lipophilicity of metal
complexes and the degree of cytotoxicity was observed.
Au(L1)Cl (1), AuPd(L1)(SC4H8)Cl3 (1a) and
Au(L2)Cl (2) [L1 = diphenylphosphino-2-pyridine;
L2 = 2-(2-(diphenylphosphino)ethyl)-pyridine] were
synthesised, in silico drug-likeness and structure–
activity relationship monitored using impedance technology.
Dose dependent changes in cytotoxicity were observed for the metal complexes resulting in IC50s of
12.5 ± 2.5, 18.3 ± 8.3 and 16.9 ± 0.5 lM for 1, 1a
and 2 respectively in an endpoint assay. When a real
time impedance assay was used, dose-dependent
responses depicting patterns that suggested slower
uptake (at a toxic 20 lM) and faster recovery of the
cells (at the less toxic 10 lM) of the bimetallic
complex (1a) compared to the monometallic complexes
(1 and 2) was observed. These data agreed with
the ADMET findings of lower aqueous solubility of 1a
and non-ideal lipophilicity (AlogP98 of 6.55) over
more water soluble 1 and 2 with ideal lipophilicity
(4.91 and 5.03 respectively) values. The additional
coordination of a Pd atom to the nitrogen atom of a
pyridine ring, the sulfur atom of a tetrahydrothiophene
moiety and two chlorine atoms in 1a could be
contributing to the observed differences when compared
to the monometallic complexes. This report
presents impedance technology as a means of correlating
drug-likeness of lipophilic phosphine complexes
containing similar backbone structures and could
prove valuable in filtering drug-like compounds in a
drug discovery project.Technology Innovation Agency (TIA), the University of Pretoria.Organization for Women in Science for the Developing World (OWSD) formerly Third World Organization for Women in Science (TWOWS) and University of Johannesburg.http://link.springer.com/journal/105342016-08-31hb201