A549 human lung carcinoma cell lines were treated with a series of new drugs with both tacrine and coumarin pharmacophores (derivatives 1a–2c) in order to test the compounds’ ability to inhibit both cancer cell growth and topoisomerase I and II activity. The ability of human topoisomerase I (hTOPI) and II to relax supercoiled plasmid DNA in the presence of various concentrations of the tacrine-coumarin hybrid molecules was studied with agarose gel electrophoresis. The biological activities of the derivatives were studied using MTT assays, clonogenic assays, cell cycle analysis and quantification of cell number and viability. The content and localization of the derivatives in the cells were analysed using flow cytometry and confocal microscopy. All of the studied compounds were found to have inhibited topoisomerase I activity completely. The effect of the tacrine-coumarin hybrid compounds on cancer cells is likely to be dependent on the length of the chain between the tacrine and coumarin moieties (1c, 1d = tacrine-(CH₂)_8–9-coumarin). The most active of the tested compounds, derivatives 1c and 1d, both display longer chains.

A combination of biochemical, biophysical and biological techniques was used to study calf thymus DNA interaction with newly synthesized 7-MEOTA-tacrine thiourea 12–17 and urea heterodimers 18–22, and to measure interference with type I and II topoisomerases. Their biological profile was also inspected in vitro on the HL-60 cell line using different flow cytometric techniques (cell cycle distribution, detection of mitochondrial membrane potential dissipation, and analysis of metabolic activity/viability). The compounds exhibited a profound inhibitory effect on topoisomerase activity (e.g. compound 22 inhibited type I topoisomerase at 1 µM concentration). The treatment of HL-60 cells with the studied compounds showed inhibition of cell growth especially with hybrids containing thiourea (14–17) and urea moieties (21 and 22). Moreover, treatment of human dermal fibroblasts with the studied compounds did not indicate significant cytotoxicity. The observed results suggest beneficial selectivity of the heterodimers as potential drugs to target cancer cells.

It is more than sixty years since the era of modern photodynamic therapy (PDT) for cancer began. Enhanced selectivity for malignant cells with a reduced selectivity for non-malignant cells and good biocompatibility along with the limited occurrence of side effects are considered to be the most significant advantages of PDT in comparison with conventional therapeutic approaches, e.g., chemotherapy. The phenomenon of multidrug resistance, which is associated with drug efflux transporters, was originally identified in relation to the application of chemotherapy. Unfortunately, over the last thirty years, numerous papers have shown that many photosensitizers are the substrates of efflux transporters, significantly restricting the effectiveness of PDT. The concept of a dynamic nanoplatform offers a possible solution to minimize the multidrug resistance effect in cells affected by PDT. Indeed, recent findings have shown that the utilization of nanoparticles could significantly enhance the therapeutic efficacy of PDT. Additionally, multifunctional nanoplatforms could induce the synergistic effect of combined treatment regimens, such as PDT with chemotherapy. Moreover, the surface modifications that are associated with nanoparticle functionalization significantly improve the target potential of PDT or chemo-PDT in multidrug resistant and cancer stem cells.