Abstract:
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.
