We report here the design, synthesis, experimental and in silico evaluation of the antibacterial and antifungal activity of some new benzo[f]quinoline derivatives. Two classes of benzo[f]quinolinium derivatives—(benzo[f]quinolinium salts (BQS) and pyrrolobenzo[f]quinolinium cycloadducts (PBQC)—were designed and obtained in two steps via a direct and facile procedure: quaternization followed by a cycloaddition reaction. The synthesized compounds were characterized by elemental and spectral analysis (FT-IR, 1H-NMR, 13C-NMR). The antimicrobial assay reveals that the BQS salts have an excellent quasi-nonselective antifungal activity against the fungus Candida albicans (some of them higher that the control drug nystatin) and very good antibacterial activity against the Gram positive bacterium Staphylococcus aureus. The PBQC compounds are inactive. Analysis of the biological data reveals interesting SAR correlations in the benzo[f]quinolinium series of compounds. The in silico studies furnished important data concerning the pharmacodynamics, pharmacokinetics and ADMET parameters of the BQS salts. Studies of the interaction of each BQS salt 3a–o with ATP synthase in the formed complex, reveal that salts 3j, 3i, and 3n have the best fit in a complex with ATP synthase. Study of the interaction of each BQS salt 3a-o with TOPO II in the formed complex reveals that salts 3j and 3n have the best-fit in complex with TOPO II. The in silico ADMET studies reveal that the BQS salts have excellent drug-like properties, including a low toxicity profile. Overall, the experimental and in silico studies indicate that compounds 3e and 3f (from the aliphatic series), respectively, and 3i, 3j and 3n (from the aromatic series), are promising leading drug candidates.

This study presents the synthesis, structural characterization, and in vitro evaluation of anticancer activity of some newly benzo[f]quinoline derivatives. The synthesis is facile and efficient, involving two steps: quaternization of nitrogen heterocycle followed by a [3+2] dipolar cycloaddition reaction. The synthesized compounds were characterized by FTIR, NMR, and X-ray diffraction on monocrystals in the case of compounds 6c and 7c. An in vitro single-dose anticancer assay of eighteen benzo[f]quinoline compounds, quaternary salts, and cycloadducts was performed. The results showed that the most active compounds were quaternary salts 3d and 3f with aromatic R substituents. Quaternary salt 3d revealed non-selective activity against all types of cancer cells, while salt 3f exhibited highly selective activity against leukemia cells. Compound 3d also presented remarkable cytotoxic efficiency against four distinct types of cancer cells—namely, non-small cell lung cancer HOP-92, melanoma LOX IMVI, melanoma SK-MEL-5, and breast cancer MDA-MB-468. The study also includes SAR correlations.

The immune system is the set of cells and organs that intervene in the body's defense against certain antigens, foreign to the body. This set includes both elements with rapid action and thus belonging to non-specific immunity, and also, elements that provide a slower response, but, with high specificity against each antigen. Nonspecific immunity sums up both cellular and humoral elements, which react quickly on foreign substances and microorganisms. On the other hand, adaptive immunity is based on the existence of lymphocytes, which develop a response, albeit slower, with a high specificity through antibodies secreted by B lymphocytes. Zinc deficiency is the second most widespread micronutrient deficiency. This compound is indispensable for the human body because it is a cofactor for many enzymes including alkaline phosphatase, dismutase superoxide, metalloproteinases. Moreover, zinc is included in the structure of growth and transcription factors and it participates in the cell communication within the immune system. Selenium is an essential trace element, being involved in many biological processes. It is part of a structural component of the amino acid selenocysteine, one of 25 selenoproteins, which are involved in the body's immune defense. Raising the awareness of iron deficiency, recent studies emphasize that it is the most common mineral deficiency worldwide. As it is already well known, iron is particularly important in the transport of oxygen, but its essential roles are not only limited to that. Besides, it is a constituent part of some metalloproteins and a cofactor for many other enzymes. Moreover, iron takes part of ATP synthesis. Therefore, the lack of iron has multiple repercussions on the whole organism, including the immune system.

No abstract