Targeted theranostics: Near-infrared triterpenoic acid-rhodamine conjugates as prerequisites for precise cancer diagnosis and therapy

F16 Hybrids Derived from Steviol or Isosteviol Are Accumulated in the Mitochondria of Tumor Cells and Overcome Drug Resistance

“…Expecting a mitochondrial accumulation of the compounds, our previously described strong mitochondria-targeted and NIR fluorescent agent/mitocan AHCS2 (compound 21 in ref. [ 4 ]) was used, thus enabling simultaneous analysis and direct comparison due to different fluorescence spectra. As shown in Figure 2 , a similar subcellular accumulation pattern of the F16 compounds and AHCS2 could be observed, proving mitochondrial accumulation.…”

“…Analysis of subcellular localization of compounds was performed in A549 cells using the established mitochondrial targeting compound AHCS2 [ 4 ] for direct comparison. For all procedures, RPMI 1640 media without phenol-red (Pan-Biotech GmbH, Aidenbach, Germany) was used.…”

“…Next, the subcellular accumulation of compounds 17 and 25 compared to 5 (F16 group) was studied, employing the fluorescent characteristics mediated by the F16 group. Expecting a mitochondrial accumulation of the compounds, our previously described strong mitochondria-targeted and NIR fluorescent agent/mitocan AHCS2 (compound 21 Representative IC 50 (in µM) values (from SRB assays) for steviol-and isosteviol-derived compounds employing A2780 ovarian carcinoma cells with respect to substitution pattern (ortho-, metaor para in the pyridinium moiety) and spacer length (2)(3)(4).…”

“…The resulting concept was successfully proven for compounds carrying, for example, a triphenylphosphonium residue [ 2 ], or a rhodamine residue connected via a suitable linker [ 3 ] or a Changsha NIR ligand [ 4 ]. Hybrids of acetylated pentacyclic triterpene carboxylic acids with (homo)-piperazinyl linkers and rhodamine residues were shown to act as mitocans.…”

“…IC 50 values in the single-digit or even sub-nanomolar nanomolar concentration range could be obtained with relatively high selectivity between malignant and non-malignant cells. Depending on the triterpene carboxylic acid used (or its degree of hydroxylation/acetylation), 2,3,23-tris-acetylated triterpene carboxylic acid derivatives interact preferentially with mitochondrial membranes with the almost complete shutdown of mitochondrial ATP synthesis, whereas with mono-acetylated analogues the conjugates could also be detected in the cell nucleus in some cases [ 4 , 5 , 6 ].…”