Screening of ferrocenyl–phosphines identifies a gold-coordinated derivative as a novel anticancer agent for hematological malignancies

Screening of ferrocenyl–phosphines identifies a gold-coordinated derivative as a novel anticancer agent for hematological malignancies

The development of new organometallic compounds as anticancer agents is currently an active area of research. Here, we report the design, synthesis and characterization of a panel of 10 new ferrocenyl–phosphine derivatives (FD1–FD10) and the analysis of their anti-proliferative activities in hematol...

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Bibliographic Details
Main Authors: Verma, Navin Kumar, Sadeer, Abdul, Kizhakeyil, Atish, Pang, Jia Hao, Tay, Shan Wen, Kumar, Pankaj, Chiu, Angela Qi Yun, Pullarkat, Sumod Appukuttan
Other Authors: School of Physical and Mathematical Sciences
Format: Article
Language:English
Published: 2019
Subjects:
Science::Chemistry
Hematological Malignancies
Anticancer Agents
Online Access:https://hdl.handle.net/10356/106352
http://hdl.handle.net/10220/49584
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Institution: Nanyang Technological University
Language: English
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Summary:The development of new organometallic compounds as anticancer agents is currently an active area of research. Here, we report the design, synthesis and characterization of a panel of 10 new ferrocenyl–phosphine derivatives (FD1–FD10) and the analysis of their anti-proliferative activities in hematolymphoid cells representing non-Hodgkin cutaneous T-cell lymphoma (CTCL). The gold-coordinated ferrocenyl–phosphine complex FD10 exhibited a significant and dose-dependent cytotoxicity in 4 different CTCL cell lines – HuT78, HH, MJ and MyLa. FD10 concentrations causing 50% cell growth inhibition (IC50) of HuT78, HH, MJ and MyLa cells at 24 h were recorded to be 5.55 ± 0.20, 7.80 ± 0.09, 3.16 ± 0.10 and 6.46 ± 0.24 μM respectively. Further mechanistic studies showed that FD10 induced apoptosis in CTCL cells by an intrinsic pathway mediated via the activation of caspase-3 and poly(ADP-ribose)polymerase. It suppressed the expression and activity of STAT3 oncoprotein in CTCL cells. FD10 caused robust G0/G1 phase cell cycle arrest and reduced the expression levels of Akt S473 phosphorylation and c-Myc, both are key cell cycle regulator proteins. Taken together, this study highlights anticancer properties of the ferrocenyl–phosphine gold organometallic complex FD10 and suggests that further development of this novel class of molecule may contribute to new drug discovery for certain hematolymphoid malignancies.

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