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@article{2418723, author = {Song, Hualong and Kostrhunová, Hana and Červinka, Jakub and Macpherson, Julie and Malina, Jaroslav and Rajan, Teena and Phillips, Roger and Postings, Miles and Shepherd, Samantha and Zhang, Xuejian and Brabec, Viktor and Rogers, Nicola J and Scott, Peter}, article_location = {Cambridge}, doi = {http://dx.doi.org/10.1039/d4sc02541e}, issn = {2041-6520}, journal = {Chemical Science}, title = {Dicobalt(II) helices kill colon cancer cells <i>via</i> enantiomer-specific mechanisms; DNA damage or microtubule disruption}, year = {2024} }
TY - JOUR ID - 2418723 AU - Song, Hualong - Kostrhunová, Hana - Červinka, Jakub - Macpherson, Julie - Malina, Jaroslav - Rajan, Teena - Phillips, Roger - Postings, Miles - Shepherd, Samantha - Zhang, Xuejian - Brabec, Viktor - Rogers, Nicola J - Scott, Peter PY - 2024 TI - Dicobalt(II) helices kill colon cancer cells <i>via</i> enantiomer-specific mechanisms; DNA damage or microtubule disruption JF - Chemical Science PB - Royal Society of Chemistry SN - 20416520 N2 - Highly diastereoselective self-assembly reactions give both enantiomers (Lambda and Delta) of anti-parallel triple-stranded bimetallic Co(ii) and Co(iii) cationic helices, without the need for resolution; the first such reaction for Co. The complexes are water soluble and stable, even in the case of Co(ii). Studies in a range of cancer and healthy cell lines indicate high activity and selectivity, and substantial differences between enantiomers. The oxidation state has little effect, and correspondingly, Co(iii) compounds are reduced to Co(ii) e.g. by glutathione. In HCT116 colon cancer cells the Lambda enantiomer induces dose-dependent G2-M arrest in the cell cycle and disrupts microtubule architectures. This Co(ii) Lambda enantiomer is ca. five times more potent than the isostructural Fe(ii) compound. Since the measured cellular uptakes are similar this implies a higher affinity of the Co system for the intracellular target(s); while the two systems are isostructural they have substantially different charge distributions as shown by calculated hydrophobicity maps. In contrast to the Lambda enantiomer, Delta-Co(ii) induces G1 arrest in HCT116 cells, efficiently inhibits the topoisomerase I-catalyzed relaxation of supercoiled plasmid DNA, and, unlike the isostructural Fe(ii) system, causes DNA damage. It thus seems very likely that redox chemistry plays a role in the latter. ER -
SONG, Hualong, Hana KOSTRHUNOVÁ, Jakub ČERVINKA, Julie MACPHERSON, Jaroslav MALINA, Teena RAJAN, Roger PHILLIPS, Miles POSTINGS, Samantha SHEPHERD, Xuejian ZHANG, Viktor BRABEC, Nicola J ROGERS and Peter SCOTT. Dicobalt(II) helices kill colon cancer cells \&{}lt;i\&{}gt;via\&{}lt;/i\&{}gt; enantiomer-specific mechanisms; DNA damage or microtubule disruption. \textit{Chemical Science}. Cambridge: Royal Society of Chemistry, 2024, 9 pp. ISSN~2041-6520. Available from: https://dx.doi.org/10.1039/d4sc02541e.
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