Improving the anticancer activity of platinum(iv) prodrugs using a dual-targeting strategy with a dichloroacetate axial ligand

Abstract

Complex 1b could release complex B and DCA, playing a dual-targeting anti-tumor effect against cancer cells, targeting nuclear DNA and mitochondria, respectively.

Dichloroacetyl Amides of 3,5-Bis(benzylidene)-4-piperidones Displaying Greater Toxicity to Neoplasms than to Non-Malignant Cells

“…The unsaturated ketones 1a-l, 2a,b were prepared by a literature procedure [2]. Copies of the 1 H and 13 C NMR spectra as well as the mass spectra of the compounds in series 1 and 2 are presented in the Supplemental Section of this report. 1 H and 13 C NMR spectra were determined in either CDCl 3 or DMSO-d 6 using a Bruker Avance III 500 MHz NMR spectrometer (Chicago, IL, USA), while mass spectra were generated using a JEOL JMS-T100GCv AccuTOF-GCv4G Mass Spectrometer (Peabody, MA, USA).…”

“…The 1 H, 13 C NMR spectra and mass spectra of compounds in series 1 and 2 are available in the Supplementary section of this article.…”

“…There are growing interests in the development of new approaches focused on creating DCA derivatives, including enhanced tolerability, safety, and the ability to cross cellular membranes, thereby facilitating drug uptake. During the last decade, many DCA derivatives of natural products [6][7][8][9], synthetic organics [10,11], and inorganic compounds [12,13] have been synthesized and evaluated for anticancer activity. For example, amides and esters of DCA and structurally related naturally occurring compounds such as albiziabioside A [6], doxorubicin [7], phenstatin [8], and honokiol [9] have been investigated in vitro against various cancer cells.…”

Pt(II) versus Pt(IV) in Carbene Glycoconjugate Antitumor Agents: Minimal Structural Variations and Great Performance Changes

“…This study allows a rather rare “true” comparison within the Pt(II)/Pt(IV) analogues. 18 − 21 In fact, while literature data widely demonstrated that Pt(IV) pro-drugs are competitive with Pt(II) agents, 22 − 37 it should be underlined that the transition to the higher oxidation state involves large structural variations (e.g., from square-planar to octahedral geometry), which makes a direct comparison between analogous Pt(IV) and Pt(II) compounds less homogeneous and more difficult to interpret. Therefore, the availability of species in the two different states of oxidation, but with an overlapping coordination environment, would provide an unprecedented opportunity to fill this gap.…”

“…Since fine modulations in the chemical properties of the investigated glucoconjugated Pt­(II)-based carbene compounds are associated with significant differences in their biological properties, we have planned to verify the consequences of the change in the oxidation state of Pt on the biological activity of these compounds, preparing Pt­(IV) analogues. This study allows a rather rare “true” comparison within the Pt­(II)/Pt­(IV) analogues. − In fact, while literature data widely demonstrated that Pt­(IV) pro-drugs are competitive with Pt­(II) agents, − it should be underlined that the transition to the higher oxidation state involves large structural variations (e.g., from square-planar to octahedral geometry), which makes a direct comparison between analogous Pt­(IV) and Pt­(II) compounds less homogeneous and more difficult to interpret. Therefore, the availability of species in the two different states of oxidation, but with an overlapping coordination environment, would provide an unprecedented opportunity to fill this gap.…”