Fluorine-containing heterocycles continue to receive considerable attention due to their unique properties. In medicinal chemistry, the incorporation of fluorine in small molecules imparts a significant enhancement their biological activities compared to non-fluorinated molecules. In this short review, we will highlight the importance of incorporating fluorine as a basic appendage in benzothiazole and benzimidazole skeletons. The chemistry and pharmacological activities of heterocycles containing fluorine during the past years are compiled and discussed.

A novel series of 2-(aryldiazenyl)-3-methyl-1H-benzo[g]indole derivatives (3a–f) were prepared through the cyclization of the corresponding arylamidrazones, employing polyphosphoric acid (PPA) as a cyclizing agent. All of the compounds (3a–f) were characterized using ¹H NMR, ¹³C NMR, MS, elemental analysis, and melting point techniques. The synthesized compounds were evaluated for cytotoxic activity against diverse human cancer cell lines by the National Cancer Institute. While all of the screened compounds were found to be cytotoxic at a 10 µM concentration, two of them (2c) and (3c) were subjected to five dose screens and showed a significant cytotoxicity and selectivity.

To design new compounds suitable as starting points for anticancer drug development, we have synthesized a novel series of benzoxazoles with pharmaceutically advantageous piperazine and fluorine moieties attached to them. The newly synthesized benzoxazoles and their corresponding precursors were evaluated for cytotoxicity on human A-549 lung carcinoma cells and non-cancer HepaRG hepatocyes. Some of these new benzoxazoles show potential anticancer activity, while two of the intermediates show lung cancer selective properties at low concentrations where healthy cells are unaffected, indicating a selectivity window for anticancer compounds.

A series of benzimidazole derivatives 8a–h were synthesized in acceptable yield and characterized by spectroscopic methods such as ¹H-NMR, ¹³C-NMR, MS, and Elemental analysis. In the urease inhibitory assay, all 8a–h showed higher urease inhibition activity (IC₅₀: 5.85–20.82 µM) in comparison to thiourea and hydroxyurea as standard (IC₅₀: 22 and 100 µM respectively). 8g exhibited the best activity with the IC₅₀ value of 5.85 µM. The docking study represented a possible mode of interaction between 8g and the active site. To investigate the cytotoxicity of the synthesized compounds, an MTT assay was performed on two different cell lines which showed 8a–h have IC50 values higher than 50 µM on both tested cell lines. 8a–h were checked for antibacterial activity and the best activity was found by 8d against Helicobacter pylori with an inhibition zone of 20 mm even stronger than gentamicin with an inhibition zone of 18 mm. Graphical Abstract

Herein, we synthesized a series of novel benzimidazole derivatives 5a–k and screened their bioactivity as potent urease inhibitors. The structure of the 5a–k was elucidated using spectroscopic technics (¹H-NMR, ¹³C-NMR, MS), elemental analysis, and melting point. The urease inhibition activity was evaluated using the urease enzyme inhibition kit. All 5a–k, except 5d, showed higher urease inhibition activity (0.77 to 6.25 µM) in comparison to thiourea and hydroxyurea as standard (IC50: 22 and 100 µM respectively). 5c and 5j exhibited the best activity with the IC50 value of 0.77 and 1.26 µM respectively. A molecular docking study showed the mode of interactions between the most active compound and enzyme active site. To investigate the cytotoxicity profile of the target compounds, an MTT assay was done on two different cell lines which showed all 5a–k have IC50 values higher than 50 µM on both tested cell lines. Graphical Abstract