Zinc, copper and nickel derivatives of 2-[2-bromoethyliminomethyl]phenol as topoisomerase inhibitors exhibiting anti-proliferative and anti-metastatic properties

Abstract

Transition metal (Zn, Cu and Ni) derivatives of (2-[2-bromoethyliminomethyl]phenol), were found to inhibit topoisomerase I activity, induce DNA cleavage and bind to calf thymus DNA. The compounds are also cytotoxic and anti-invasive against PC3.

Copper Complexes as Anticancer Agents Targeting Topoisomerases I and II

“…Salicylidene-Cu(II) derivative 9 of 2-[2-bromoethyliminomethyl] phenol [ 83 , 84 ] is a bifunctional drug that inhibits both cancer cell growth and metastasis.…”

Two dpa-based zinc(ii) complexes as potential anticancer agents: nuclease activity, cytotoxicity and apoptosis studies

“…28 Recent studies provided compelling evidence that Zn(II) derivatives have proved to be potential anticancer agents with low in vivo toxicity, low side effects and perhaps new modes of action and cellular targets compared with the classical metallodrugs. [29][30][31][32][33][34][35][36] Apart from the choice of metal ions, design of these metalbased pharmaceuticals depends on the ligand framework. Ligands can significantly alter the biological properties by modifying reactivity or substitution inertness, including limiting the adverse effects of metal ion overload, inhibiting selected metalloenzymes, and facilitating metal ion redistribution.…”

Zinc Complexes with Nitrogen Donor Ligands as Anticancer Agents

“…), with obvious advantages for bio-compatibility [ 47 , 48 , 49 , 50 , 51 ]; (3) Zn(II) complexes probably have targets and mechanisms of action different from the classical platinum-based drugs [ 52 , 53 , 54 , 55 ]; (4) zinc is one of the most studied metals in the coordination of photosensitive systems metals for Photo Dynamic Therapy (PDT) [ 56 , 57 , 58 ], and (5) due to their ability to assist Lewis activation, nucleophile formation and rapid ligand exchange, zinc compounds can be employed as catalysts of hydrolytic reactions, such as hydrolysis and DNA cleavage, thus making anti-tumor activity possible [ 59 , 60 ]. Recent studies have confirmed the above assumptions showing that Zn(II) derivatives could be potential anticancer agents with low toxicity in vivo, low side effects and probably different cellular targets and modes of action when compared with classical metal-based drugs [ 53 , 55 , 61 , 62 , 63 , 64 , 65 , 66 ].…”