Cancer and malaria are both global health threats. Due to the increase in the resistance to the known drugs, research on new active substances is a priority. Here, we present the design, synthesis, and evaluation of the biological activity of harmicens, hybrids composed of covalently bound harmine/β-carboline and ferrocene scaffolds. Structural diversity was achieved by varying the type and length of the linker between the β-carboline ring and ferrocene, as well as its position on the β-carboline ring. Triazole-type harmicens were prepared using Cu(I)-catalyzed azide-alkyne cycloaddition, while the synthesis of amide-type harmicens was carried out by applying a standard coupling reaction. The results of in vitro biological assays showed that the harmicens exerted moderate antiplasmodial activity against the erythrocytic stage of P. falciparum (IC₅₀ in submicromolar and low micromolar range) and significant and selective antiproliferative activity against the MCF-7 and HCT116 cell lines (IC₅₀ in the single-digit micromolar range, SI > 5.9). Cell localization experiments showed different localizations of nonselective harmicene 36 and HCT116-selective compound 28, which clearly entered the nucleus. A cell cycle analysis revealed that selective harmicene 28 had already induced G1 cell cycle arrest after 24 h, followed by G2/M arrest with a concomitant drastic reduction in the percentage of cells in the S phase, whereas the effect of nonselective compound 36 on the cell cycle was much less pronounced, which agreed with their different localizations within the cell.

Epithelial-to-mesenchymal transition (EMT) gives rise to cells with properties similar to cancer stem cells (CSCs). Targeting the EMT program to selectively eliminate CSCs is a promising way to improve cancer therapy. Salinomycin (Sal), a K+/H+ ionophore, was identified as highly selective towards CSC-like cells, but its mechanism of action and selectivity remains elusive. Here, we show that Sal, similar to monensin and nigericin, disturbs the function of the Golgi. Sal alters the expression of Golgi-related genes and leads to marked changes in Golgi morphology, particularly in cells that have undergone EMT. Moreover, Golgi-disturbing agents severely affect post-translational modifications of proteins, including protein processing, glycosylation and secretion. We discover that the alterations induced by Golgi-disturbing agents specifically affect the viability of EMT cells. Collectively, our work reveals a novel vulnerability related to the EMT, suggesting an important role for the Golgi in the EMT and that targeting the Golgi could represent a novel therapeutic approach against CSCs.

As a result of our previous research focussed on benzimidazoles, herein we present design, synthesis, QSAR analysis and biological activity of novel N-substituted benzimidazole derived carboxamides. Carboxamides were designed to study the influence of the number of methoxy groups, the type of the substituent placed at the benzimidazole core on biological activity. Pronounced antioxidative activity displayed unsubstituted 28 (IC₅₀ ≈ 3.78 mM, 538.81 mmolFe²⁺/mmolC) and dimethoxy substituted derivative 34 (IC₅₀ ≈ 5.68 mM, 618.10 mmolFe²⁺/mmolC). Trimethoxy substituted 43 and unsubstituted compound 40 with isobutyl side chain at N atom showed strong activity against HCT116 (IC₅₀ ≈ 0.6 µM, both) and H 460 cells (IC₅₀ ≈ 2.5 µM; 0.4 µM), being less cytotoxic towards non-tumour cell. Antioxidative activity in cell generally confirmed relatively modest antioxidant capacity obtained in DPPH/FRAP assays of derivatives 34 and 40. The 3D-QSAR models were generated to explore molecular properties that have the highest influence on antioxidative activity.

Multidrug resistance (MDR) poses a significant challenge in cancer therapy, often leading to treatment failure and relapse. ATP-binding cassette (ABC) transporters, particularly ABCG2, play a pivotal role in MDR development by actively expelling chemotherapeutic agents from cancer cells. This study investigates the effects of two groups of primaquine derivatives—fumardiamides (1a–d) and bis-ureas (2a, b), both bearing halogenated benzene rings—on the activity of P-glycoprotein (P-gp) and ABCG2. Their potential to reverse MDR was evaluated through a series of functional assays aimed at comparing transporter–compound interactions. The results indicated that fumardiamide derivatives, specifically 1a, 1b, and 1d, exhibited potent inhibition of ABCG2 while having no effect on P-gp, demonstrating a selective mode of action. The tested derivatives displayed low to moderate cytotoxicity and did not affect ABCG2 expression or localization. Moreover, these compounds enhanced the sensitivity of drug-resistant cancer cell lines to mitoxantrone, underscoring their potential to overcome ABCG2-mediated MDR. These findings suggest that chemical modifications of primaquine, particularly the incorporation of fumardiamide moieties, confer novel biological properties, providing promising leads for the development of selective ABCG2 inhibitors.

Five copper-(II) coordination polymerstrans-[Cu-(μ-l-hser)-(l-hser)] _n (1a), {cis-[Cu-(μ-l-hser)₂]·H₂O} _n (1b·H₂O), {[Cu-(μ-l-hser)-(H₂O)-(bpy)]₂SO₄·2H₂O} _n (2·2H₂O), {[Cu-(μ-l-hser)-(H₂O)-(bpy)]₂SO₄·3H₂O} _n (2·3H₂O), and {[Cu-(μ-l-hser)-(H₂O)-(bpy)]₂SO₄·4H₂O} _n (2·4H₂O)were synthesized via solution-based and/or mechanochemical methods (l-hser = l-homoserinate, bpy = 2,2'-bipyridine). The compounds were characterized in the solid state (using single-crystal and powder X-ray diffraction (SCXRD and PXRD), EPR, Raman and IR spectroscopy, and thermogravimetric analysis (TGA)) and in solution (using UV-vis spectroscopy, EPR, Raman spectroscopy, and fluorimetry). In the binary bis-(homoserinato)-copper-(II) compounds, 1a and 1b·H₂O, polymerization is achieved through the hydroxyl group of the l-homoserinate side chain. In contrast, all ternary compounds (2·2H₂O, 2·3H₂O, and 2·4H₂O) achieved polymerization through the carboxylate group of l-homoserinate. Successful solid-state transformation of 2·2H₂O into 2·4H₂O was established at higher relative humidity values. Copper-(II) centers adopt a square-pyramidal geometry in 1a and a distorted octahedral geometry in all other investigated compounds. Spectroscopic studies suggest that 1a retains its solid-state geometry in solution, while 2·2H₂O and 2·3H₂O exhibit slight changes. Among the compounds, 2·2H₂O exhibited moderate antiproliferative activity against H460 (lung), MCF-7 (breast), and HCT116 (colon) cancer cell lines, and demonstrated antibacterial activity against Moraxella catarrhalis ATCC 23246. Absorption and fluorescence spectra suggested a lower binding affinity of 2·2H₂O to the double-stranded DNA dodecamer ds-(CGCGAATTCGCG).