Screening of ferrocenyl–phosphines identifies a gold-coordinated derivative as a novel anticancer agent for hematological malignancies. Issue 51 (14th August 2018)

• Record Type: Journal Article
• Authors: Verma, Navin Kumar; Sadeer, Abdul; Kizhakeyil, Atish; Pang, Jia Hao; Angela Chiu, Qi Yun; Tay, Shan Wen; Kumar, Pankaj; Pullarkat, Sumod A.
• Is Part Of: RSC advances. Volume 8:Issue 51(2018)
• Page Start: 28960
• Page End: 28968
• Publication Date: 2018-08-14
• Subjects: Chemistry -- Periodicals; 540.5
• DOI: 10.1039/c8ra05224g
• Languages: English
• ISSNs: 2046-2069

Abstract

Abstract : Development of organometallic compounds as novel anticancer agents. Abstract : 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 complexFD10 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 thatFD10 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 complexFD10 and suggests that further development of this novel class of molecule may contribute to new drug discovery for certain hematolymphoid malignancies.