Metallohelices emulate the properties of short cationic α-helical peptides

Abstract

Advances in metal–organic self-assembly have unearthed an area of chemical space containing peptide-emulating molecules. Comparison with natural systems indicates future directions in terms of synthesis, disease areas and mechanistic understanding.

Cavity-Containing [Fe2L3]4+ Helicates: An Examination of Host-Guest Chemistry and Cytotoxicity

“…However, the low μM activity observed for [Fe 2 ( L1 ) 3 ](BF 4 ) 4 suggests that it could be more active than the [Fe 2 ( L Pyim ) 3 ] 4+ helicates (IC 50 values ranged from 19–52 μM, despite having been determined in different cell lines) ( Hotze et al, 2008 ). The observed activity of [Fe 2 ( L1 ) 3 ](BF 4 ) 4 is similar in magnitude to that found by Scott et al for their family of [Fe 2 ( L pyimR ) 3 ] 2+ helicates ( Song et al, 2021 ). However, the [Fe 2 ( L pyimR ) 3 ] 2+ systems are more effective overall with some of that family displaying nanomolar activities ( Kaner et al, 2016 ; Song et al, 2020 ).…”

“…Related [Fe 2 L 3 ] 4+ helicates have shown excellent anticancer activity (Song et al, 2021 Due to the modest water solubility of many drug candidates, it is common to use DMSO to solubilize compounds for cytotoxicity experiments. However, it is also well known that DMSO can displace coordinated ligands and decompose metal complexes (Patra et al, 2013;Vellas et al, 2013;Hall et al, 2014;Huang et al, 2017).…”

“…Related [Fe 2 L 3 ] 4+ helicates have shown excellent anticancer activity ( Song et al, 2021 ). Therefore, we examined the cytotoxicity of [Fe 2 ( L1 ) 3 ] 4+ and [Fe 2 ( L2 ) 3 ] 4+ against a panel of cancer cell lines.…”

“…Like the parent Hannon helicate, it has been shown that these new pyridylimine-based complexes have shown a diverse range of biological properties and some flexicates have impressive, tunable anti-microbial ( Howson et al, 2012 ; Simpson et al, 2019 ) and anti-cancer ( Brabec et al, 2013 ; Faulkner et al, 2014 ; Kaner and Scott, 2015 ; Kaner et al, 2016 ; Song et al, 2019 ; Song et al, 2020 ) properties. The interactions of this more diverse family of helicates with DNA/RNA ( Song et al, 2021 ) and proteins ( Li et al, 2014 ) have also been examined and the systems show structure-dependent binding to duplex DNA ( Brabec et al, 2013 ; Malina et al, 2015b ), G-quadruplexes ( Zhao et al, 2017 ; Zhao et al, 2018 ), 3WJ and 4WJ ( Brabec et al, 2013 ), and bulges ( Malina et al, 2015a ; Hrabina et al, 2020 ).…”

FeII Metallohelices Stabilize DNA G‐Quadruplexes and Downregulate the Expression of G‐Quadruplex‐Regulated Oncogenes

“…The results show that the studied metallohelices bind with high affinity to G4 DNA while exhibiting much lower affinity towards duplex DNA. We consider that the remarkably strong and selective binding of these supramolecular architectures 5 a – h is part of a growing body of evidence that metallohelices, by nature of their similar shape, size, charge and amphipathic nature, emulate the properties of short peptidic α‐helices [21a] …”