A multi-target caffeine derived rhodium(i) N-heterocyclic carbene complex: evaluation of the mechanism of action

Abstract

A rhodium(i) and a ruthenium(ii) complex with a caffeine derived N-heterocyclic carbene (NHC) ligand were biologically investigated as organometallic conjugates consisting of a metal center and a naturally occurring moiety. While the ruthenium(ii) complex was largely inactive, the rhodium(i) NHC complex displayed selective cytotoxicity and significant anti-metastatic and in vivo anti-vascular activities and acted as both a mammalian and an E. coli thioredoxin reductase inhibitor. In HCT-116 cells it increased the reactive oxygen species level, leading to DNA damage, and it induced cell cycle arrest, decreased the mitochondrial membrane potential, and triggered apoptosis. This rhodium(i) NHC derivative thus represents a multi-target compound with promising anti-cancer potential.

Metal NHC Complexes with Naphthalimide Ligands as DNA‐Interacting Antiproliferative Agents

“…For copper NHC complexes lipophilicity appears to play an important role for obtaining active antiproliferative complexes. Inactivity of some ruthenium NHC complexes in cytotoxicity experiments had been observed in previous studies and was probably the consequence of a low bioavailability …”

Small molecule inhibitors of mammalian thioredoxin reductase as potential anticancer agents: An update

“…The complex 179 acted as both an Escherichia coli and a mammalian TrxR inhibitor, and displayed remarkable antivascular and antimetastatic functions. The complex 179 inhibited TrxR with IC 50 values of 3.64 μM, which might account for its pharmacological functions . Lanthanum chloride (LaCl 3 ) ( 180 , Figure ) was reported by Bindoli and co‐workers, which is a good inhibitor of both the cytosolic TrxR1 and mitochondrial TrxR2 with IC 50 values of 1.75 and 7.46 μM, respectively.…”

Ein Multitarget‐Gold(I)‐Komplex induziert Zytotoxizität im Zusammenhang mit Aneuploidie in HCT‐116‐Kolorektalkarzinomzellen

“…[2] Alkinylliganden haben sich in letzter Zeit als vielversprechende Komponenten von Wirkstoffen auf Goldbasis herausgestellt, jedoch wurden die daraus resultierenden Alkinylgold(I)-Verbindungen viel seltener fürt herapeutische Anwendungen untersucht als andere Goldkomplexe. [3,4] Basierend auf früheren Arbeiten zu vielversprechenden Metallwirkstoffen mit Xanthinliganden [5,6] ist die Alkinylgruppe in den hier beschriebenen Zielverbindungen an eine Coffein-Te ilstruktur gebunden (Abbildung 1).…”