Design, synthesis and high antitumor potential of new unsymmetrical bisacridine derivatives towards human solid tumors, specifically pancreatic cancers and their unique ability to stabilize DNA G-quadruplexes

The Influence of Antitumor Unsymmetrical Bisacridines on 3D Cancer Spheroids Growth and Viability

“…C-2028 was more potent in this research than was the C-2045 derivative; however, the same dosage of drugs was used in the mice treatment, although C-2045 exhibited lower cytotoxicity and underwent glucuronidation, which might have decreased the effective drug concentrations in mice [ 28 ]. The therapeutic effectiveness of the four bisacridine derivatives was also evaluated in the panel of several human tumor xenografts in nude mice [ 13 ]. All the compounds, including C-2041, displayed high tumor growth inhibition index (TGI) values, especially against pancreatic cancer cells, such as PANC-1, Mia-Pa-Ca-2, BxPC-3, and other cell lines, which are characterized by slow growth rates.…”

“…Only the antitumor potency of C-2028 was assessed in HCT116 and H460 xenografts (fast tumor growth), and the compound inhibited the growth of tumors by around 30%, which was much weaker than in experiments with pancreatic cells. It is worth mentioning that, although C-2041 managed to stop the growth of xenografts to a similar extent to the other tested derivatives, it displayed very low maximal tolerated doses, suggesting high toxicity for this compound, which may result in difficulties in the usage of this compound in clinics [ 13 ].…”

“…Spheroids have been widely used for the in vitro biological evaluation of antitumor compounds; therefore, we decided to apply this culture model in our studies concerning unsymmetrical bisacridines (UAs) ( Figure 1 ). This is a group of new, promising antitumor compounds among acridine derivatives, which has been patented in Europe and the USA [ 11 , 12 ], exhibiting high cytotoxic and antitumor activity against numerous cancers, including human lung and colorectal cancers [ 13 ]. They exhibited high cytotoxic activity against a set of 14 human tumor cell lines and antitumor activity against numerous xenografts in nude mice, including human lung and colorectal cancers, and also against Walker 256 adenocarcinoma in rats [ 13 ].…”

“…This is a group of new, promising antitumor compounds among acridine derivatives, which has been patented in Europe and the USA [ 11 , 12 ], exhibiting high cytotoxic and antitumor activity against numerous cancers, including human lung and colorectal cancers [ 13 ]. They exhibited high cytotoxic activity against a set of 14 human tumor cell lines and antitumor activity against numerous xenografts in nude mice, including human lung and colorectal cancers, and also against Walker 256 adenocarcinoma in rats [ 13 ]. Two of the UA compounds, C-2028 and C-2045, were shown to induce apoptosis in HCT116 and H460 cells and accelerated senescence only in H460 cells [ 14 ].…”

Quantum Dots as a Good Carriers of Unsymmetrical Bisacridines for Modulating Cellular Uptake and the Biological Response in Lung and Colon Cancer Cells

“…Unsymmetrical bisacridine derivatives (UAs), new anticancer compounds synthesized in our laboratory, were non-covalently attached to non-toxic QDs (Ag-In-Zn-S nanocrystals). These compounds exhibited high cytotoxic activity-principally against human pancreatic, lung, and colon cancer cells-as well as demonstrated high antitumor activity, preferentially against pancreatic cancer xenografts of human origin [19][20][21].…”