MilliporeSigma
  • Home
  • Search Results
  • Conjugation of cisplatin analogues and cyclooxygenase inhibitors to overcome cisplatin resistance.

Conjugation of cisplatin analogues and cyclooxygenase inhibitors to overcome cisplatin resistance.

ChemMedChem (2014-10-17)
Wilma Neumann, Brenda C Crews, Menyhárt B Sárosi, Cristina M Daniel, Kebreab Ghebreselasie, Matthias S Scholz, Lawrence J Marnett, Evamarie Hey-Hawkins
ABSTRACT

Cyclooxygenase (COX) is an enzyme involved in tumorigenesis and is associated with tumor cell resistance against platinum-based antitumor drugs. Cisplatin analogues were conjugated with COX inhibitors (indomethacin, ibuprofen) to study the synergistic effects that were previously observed in combination treatments. The conjugates ensure concerted transport of both drugs into cells, and subsequent intracellular cleavage enables a dual-action mode. Whereas the platinum(II) complexes showed cytotoxicities similar to those of cisplatin, the platinum(IV) conjugates revealed highly increased cytotoxic activities and were able to completely overcome cisplatin-related resistance. Although some of the complexes are potent COX inhibitors, the conjugates appear to execute their cytotoxic action via COX-independent mechanisms. Instead, the increased lipophilicity and kinetic inertness of the conjugates seem to facilitate cellular accumulation of the platinum drugs and thus improve the efficacy of the antitumor agents. These conjugates are important tools for the elucidation of the direct influence of COX inhibitors on platinum-based anticancer drugs in tumor cells.

MATERIALS
Product Number
Brand
Product Description

Sigma-Aldrich
Nitric acid, 70%, purified by redistillation, ≥99.999% trace metals basis
Sigma-Aldrich
Nitric acid, ACS reagent, ≥90.0%
Sigma-Aldrich
Arachidonic acid, from non-animal source, ≥98.5% (GC)
Supelco
Nitric acid concentrate, 0.1 M HNO3 in water (0.1N), eluent concentrate for IC
Sigma-Aldrich
Arachidonic acid, >95.0% (GC)
Sigma-Aldrich
Nitric acid, puriss. p.a., reag. ISO, reag. Ph. Eur., for determinations with dithizone, ≥65%
Sigma-Aldrich
Nitric acid, puriss. p.a., 65.0-67.0%
Sigma-Aldrich
Nitric acid, puriss. p.a., ≥65% (T)
Sigma-Aldrich
Nitric acid, red, fuming, HNO3 >90 %
Sigma-Aldrich
Nitric acid, ACS reagent, 70%
Sigma-Aldrich
Mercury, electronic grade, 99.9999% trace metals basis
Sigma-Aldrich
Mercury, ACS reagent, 99.9995% trace metals basis
Sigma-Aldrich
Mercury, ≥99.99% trace metals basis
Sigma-Aldrich
Nitric-14N acid solution, ~10 N in H2O, 99.99 atom % 14N