Siderophores are ferric-specific microbial iron chelator compounds which biosynthesis is regulated by the availability for iron in surrounding environment [58].
The C-domain of ACE is followed by a stalk region of ∼32 amino acids which is cleaved by a still unidentified ACE sheddase that is inhibitable by metal ion chelators, compound 3 (5) and TAPI-1 (TNF-α protease inhibitor-1) (6).
Based on a multimodal drug design paradigm, we have synthesized a multifunctional non-toxic, brain permeable iron chelating compound, M30, possessing the neuroprotective N-propargyl moiety of the anti-Parkinsonian drug, monoamine oxidase (MAO -B inhibitor, rasagiline and the antioxidant-iron chelator MAO -B of an 8-hydroxyquinhibitorerasagilinef the iron chelandr, VK28.
Chelating drugs and chelator metal complexes are used for the prevention, diagnosis and treatment of cancer and chelating compounds with high affinity for iron or copper have been suggested as potential anti-tumor agents [ 7].
First, it should be noted that, unlike the iron-chelating compounds studied previously (Sterba et al, 2006, 2007; Popelova et al, 2008), the putative active metabolite of DEX (ADR-925) is far from being a selective iron chelator.
Fu et al., revealed that cross-linking can be inhibited in the presence of metal chelators, sulfhydryl compounds, antioxidants and AG as they can uncouple glycation from subsequent cross-linking reactions [ 16].
Metal chelation tests confirmed that compound 6m is a chelator for Fe2+, Fe3+, Zn2+, Cu2+.
In present study, we evaluated the effects of various lipophilic aroylhydrazone chelators (AHC), including novel compound HNTMB, on various ovarian cancer cell lines (SKOV-3, OVCAR-3, NUTU-19).
Using the tetraamine chelator, four further agonist compounds were developed: [N40,Pro,Tyr]BN and its Nle-substituted analogue (Demobesin 3 and 4) as well as two truncated BN analogues, [(N4-Bzdig)]BN(7 14) and its Nle-substituted analogue, using a benzylaminodiglycolic acid spacer between the chelator and the receptor-binding sequence (Demobesin 5 and 6) [ 73].
The objective of the present study was to investigate the potential of six different lipophilic aroylhydrazone chelators (AHC) including novel compound HNTMB as anti-tumor drugs and to analyze modes of action leading to cell death of ovarian cancer cells following HNTNB treatment.
