Silver(I) N‑Heterocyclic Carbene Complexes
Derived from Clotrimazole: Antiproliferative Activity and Interaction
with an Artificial Membrane-Based Biosensor
posted on 2020-03-19, 21:45authored byHeba A. Mohamed, Samantha Shepherd, Nicola William, Helen A. Blundell, Madhurima Das, Christopher M. Pask, Benjamin R. M. Lake, Roger M. Phillips, Andrew Nelson, Charlotte E. Willans
With the aim of combining
the potential anticancer properties of
both clotrimazole, an imidazole based antifungal agent, and silver(I)
N-heterocyclic carbenes, 13 novel silver(I) N-heterocyclic carbene
complexes derived from clotrimazole were synthesized. The complexes
were fully characterized, and the partition coefficient of each was
determined to provide a measure of hydrophobicity. The antiproliferative
properties of the complexes against cancerous and noncancerous cell
lines found optimum cytotoxicity when the complex displays an “intermediate
lipophilicity”, which describes a complex that possesses both
water-soluble groups and lipophilic aromatic groups. The silver complexes
were screened on a synthetic biomembrane-like device using a chip-based
phospholipid-coated Pt/Hg electrode embedded in a flow cell system.
The results are recorded as rapid cyclic voltammograms (RCVs), which
give insight into the interactions of the complexes with a cell membrane.
Interestingly the principle of “intermediate lipophilicity”
also applies to the monolayer interaction to which the silver atom
significantly implements an irreversibility.