In this study, new 7-chloro-4-aminoquinoline-benzimidazole compounds were synthesized and characterized by NMR, MS, and elemental analysis. These novel hybrids differ in the type of linker and in the substituent on the benzimidazole moiety. Their antiproliferative activities were evaluated on one non-tumor (MDCK1) and seven selected tumor (CaCo-2, MCF-7, CCRF-CEM, Hut78, THP-1, and Raji) cell lines by MTT test and flow cytometry analysis. The compounds with different types of linkers and an unsubstituted benzimidazole ring, 5d, 8d, and 12d, showed strong cytotoxic activity (the GI50 ranged from 0.4 to 8 µM) and effectively suppressed the cell cycle progression in the leukemia and lymphoma cells. After 24 h of treatment, compounds 5d and 12d induced the disruption of the mitochondrial membrane potential as well as apoptosis in HuT78 cells. The drug-like properties and bioavailability of the compounds were calculated using the Swiss ADME web tool, and a molecular docking study was performed on tyrosine-protein kinase c-Src (PDB: 3G6H). Compound 12d showed good solubility and permeability and bound to c-Src with an energy of −119.99 kcal/mol, forming hydrogen bonds with Glu310 and Asp404 in the active site and other residues with van der Waals interactions. The results suggest that compound 12d could be a leading compound in the further design of effective antitumor drugs.

This work reports the preparation of amino acid-functionalized CQDs from citric acid by facile hydrothermal synthesis. The prepared N-doped CQDs exhibited excellent optical, physical, and chemical properties, and the differences were observed among the six different amino acids used as nitrogen dopants (Leu, Trp, Lys, Arg, Ala, His). Compared to the blank sample (without the addition of amino acids), N-doped CQDs have shown significantly higher quantum yield, also demonstrating the potential in metal ion sensing. The highest quantum yield of 36.45%, with a peak excitation/emission of 340/406 nm, was achieved using citric acid and amino acid Leu (CQD@Leu), treated at temperature of 180 °C during 9 h. The prepared samples were investigated toward metal ion selectivity (Ca2+, Cu2+, Fe3+, K+, Hg2+, Mg2+, Al3+, Mn2+, and Na+), and the CQD@Leu showed a selective and sensitive response upon the addition of Fe3+ ions. Therefore, CQD@Leu was selected for further investigation in Fe3+ detection in the model system and real well water samples. A developed model was described by a logistic function with a good coefficient of determination of R2 = 0.9982, while the linear range was determined in the concentration range from 0.3 mol dm−3 to 30 mol dm−3, with a determined limit of detection of LOD = 1.77 ± 0.01 mol dm−3 and limit of quantification of LOQ = 5.89 ± 0.04 mol dm−3. Furthermore, the results of the in vitro cytotoxicity test (MTT) with normal and tumor cell lines (MRC-5, HeLa, NCI-H358, and CaCo-2) clearly demonstrate the excellent biocompatibility of CQD@Leu.

The synthesis of novel 1,1′‐disubstituted ferrocene conjugates appended with N‐1 and O‐4 alkylated quinolone and quinoline was reported. The target compounds were synthesized employing a liquid‐assisted grinding (LAG) mechanochemical method in copper‐catalyzed azide‐alkyne cycloaddition (CuAAC) to obtain ferrocene−quinoline/quinolone hybrids (5a–5d, 6a–6d, 7a, 7b, 8a, and 8b) in higher yields and shorter reaction time compared to a conventional method, thus proving superiority of mechanochemistry versus conventional synthesis. Bis‐quinoline and bis‐quinolone ferrocene derivatives were evaluated for their antiproliferative effects on five selected tumor and two non‐tumor cell lines. Bis‐6‐methylquinolone–ferrocene conjugate 8b showed the best antiproliferative effect on T‐cell lymphoma (HuT78) cells (IC50 = 14.8 μM) and no cytotoxicity on both non‐tumor MDCK1 and BJ cells. Results obtained after mitochondrial membrane potential (∆Ψm) measurement using flow cytometry showed that compound 8b caused accumulation of HuT78 cells in subG0/G1 phase, disturbance of mitochondrial membrane potential, and apoptosis. The structure of the quinolone and ferrocene hybrid 8b can be further optimized to obtain candidates with better inhibitory effects on HuT78 cells.

Syntheses of 6-halogen-substituted benzothiazoles were performed by condensation of 4-hydroxybenzaldehydes and 2-aminotiophenoles and subsequent O-alkylation with appropriate halides, whereas 6-amidino-substituted benzothiazoles were synthesized by condensation of 5-amidino-2-aminothiophenoles and corresponding benzaldehydes. While most of the compounds from non-substituted and halogen-substituted benzothiazole series showed marginal antiproliferative activity on tested tumor cell lines, amidino benzazoles exhibited stronger inhibitory activity. Generally, imidazolyl benzothiazoles showed pronounced and nonselective activity, with the exception of 36c which had a strong inhibitory effect on HuT78 cells (IC50 = 1.6 µM) without adverse cytotoxicity on normal BJ cells (IC50 >100 µM). Compared to benzothiazoles, benzimidazole structural analogs 45a–45c and 46c containing the 1,2,3-triazole ring exhibited pronounced and selective antiproliferative activity against HuT78 cells with IC50 < 10 µM. Moreover, compounds 45c and 46c containing the methoxy group at the phenoxy unit were not toxic to normal BJ cells. Of all the tested compounds, benzimidazole 45a with the unsubstituted phenoxy central core showed the most pronounced cell growth inhibition on THP1 cells in the nanomolar range (IC50 = 0.8 µM; SI = 70). QSAR models of antiproliferative activity for benzazoles on T-cell lymphoma (HuT78) and non-tumor MDCK-1 cells elucidated the effects of the substituents at position 6 of benzazoles, demonstrating their dependence on the topological and spatial distribution of atomic mass, polarizability, and van der Waals volumes. A notable cell cycle perturbation with higher accumulation of cells in the G2/M phase, and a significant cell increase in subG0/G1 phase were found in HuT78 cells treated with 36c, 42c, 45a–45c and 46c. Apoptotic morphological changes, an externalization of phosphatidylserine, and changes in the mitochondrial membrane potential of treated cells were observed as well.