PREPARATION OF NEW PLATINUM-BASED
POTENTIAL ANTICANCER DRUGS
Karolina Wawrocka,a,b Jan Chyba,a Radek Mareka,b
a
CEITEC – Central European Institute of Technology and b
Department of Chemistry,
Masaryk University, Kamenice 5/A4, CZ-62500 Brno, Czech Republic
Platinum-based drugs are the most commonly used medicines in cancer treatment.
Since the discovery of cisplatin, thousands of platinum complexes have been synthesized and
examined for anticancer activity1
. The main drawbacks of currently used antitumor medicines
are side effects and acquired or intrinsic resistance of cancer cells to drugs. To overcome their
limitations, new platinum complexes that possess structural fragments designed for
encapsulation within macrocyclic cavitands are being prepared. Orally administered,
platinum(IV) complexes have been proven to be kinetically more inert than platinum(II)
complexes and more stable to acidic media. These prodrugs can be reduced to platinum(II)
species and possess higher activity after release of the axial ligands2
. Their efficacy may be
improved by binding to carriers which help with their transport and delivery to the target
cancer cells. Encapsulation of platinum(IV) complexes within macrocyclic cavitands enables
to prevent complex degradation during transport, reduce side effects, and improve targeting3
.
In this study several novel Pt(II) and Pt(IV) complexes were synthesized. All prepared
compounds possess structural fragment to enable their encapsulation within macrocyclic
cavitands. Positively charged monofunctional Pt(II) complex containing only one labile site
for coordination to DNA was prepared and its interactions with macrocyclic cavitands were
studied by 1
H NMR spectroscopy. Various leaving groups were installed in axial positions of
cisplatin, resulting in the formation of octahedral symmetrical and unsymmetrical Pt(IV)
complexes. The compounds were characterized by 1
H and 195
Pt NMR spectroscopy, IR,
Raman, X-ray and ESI-MS measurements.
This work was supported by the Czech Science Foundation (16-05961S).
1. M. Kettunen, A. S. Abu-Surrah, Current Medicinal Chemistry, 2006, 13, 1337-1357.
2. B. R. Hoffmeister et al., Chemistry & biodiversity, 2012, 9, 1840–1848.
3. A. I. Day, J. G. Collins, Cucurbituril Receptors and Drug Delivery, in Supramolecular Chemistry: From
Molecules to Nanomaterials, 2012, 983–1000.