Synthesis and anti-cancer activity of bis-amino-phosphine ligand and its ruthenium(II) complexes

[Display omitted] •Novel arene ruthenium (II) complexes were synthesized.•These complexes hindered cellular proliferation and displayed apoptotic features in malignant A375 cells.•Complex GA113 holds potential as an alternative targeted chemotherapeutic agent. The development of both chemotherapeuti...

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Veröffentlicht in:Bioorganic & medicinal chemistry letters 2020-10, Vol.30 (20), p.127492-127492, Article 127492
Hauptverfasser: Engelbrecht, Zelinda, Roberts, Kim Elli, Hussan, Ayesha, Amenuvor, Gershon, Cronjé, Marianne Jaqueline, Darkwa, James, Makhubela, Banothile C.E., Sitole, Lungile
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Sprache:eng
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Zusammenfassung:[Display omitted] •Novel arene ruthenium (II) complexes were synthesized.•These complexes hindered cellular proliferation and displayed apoptotic features in malignant A375 cells.•Complex GA113 holds potential as an alternative targeted chemotherapeutic agent. The development of both chemotherapeutic drug resistance as well as adverse side effects suggest that the current chemotherapeutic drugs remain ineffective in treating the various types of cancers. The development of new metallodrugs presenting anti-cancer activity is therefore needed. Ruthenium complexes have gained a great deal of interest due to their promising anti-tumour properties and reduced toxicity in vivo. This study highlighted the effective induction of cell death in a malignant melanoma cell by two novel bis-amino-phosphine ruthenium(II) complexes referred to as GA105 and GA113. The IC50 concentrations were determined for both the complexes, the ligand and cisplatin, for comparison. Both complexes GA105 and GA113 displayed a high anti-cancer selectivity profile as they exhibited low IC50 values of 6.72 µM and 8.76 µM respectively, with low toxicity towards a non-malignant human cell line. The IC50 values obtained for both complexes were lower than that of cisplatin. The new complexes were more effective compared to the free ligand, GA103 (IC50 = >20 µM). Morphological studies on treated cells induced apoptotic features, which with further studies could indicate an intrinsic cell death pathway. Additionally, flow cytometric analysis revealed that the mode of cell death of complex GA113 was apoptosis. The outcomes herein give further insight into the potential use of selected Ru(II) complexes as alternative chemotherapeutic drugs in the future.
ISSN:0960-894X
1464-3405
DOI:10.1016/j.bmcl.2020.127492