The design, synthesis, structure, and in vitro anticancer and antimycobacterial activity of new hybrid imidazole (benzimidazole)/pyridine (quinoline) derivatives are described. The strategy adopted for synthesis is straight and efficient, involving a three-step setup procedure: N-acylation, N-alkylation, and quaternization of nitrogen heterocycle. The solubility in microbiological medium and anticancer and antimycobacterial activity of a selection of new synthesized compounds were evaluated. The hybrid derivatives have an excellent solubility in microbiological medium, which make them promising from the pharmacological properties point of view. One of the hybrid compounds, 9 (with a benzimidazole and 8-aminoquinoline skeleton), exhibits a very good and selective antitumor activity against Renal Cancer A498 and Breast Cancer MDA-MB-468. Moreover, the anticancer assay suggests that the hybrid Imz (Bimz)/2-AP (8-AQ) compounds present a specific affinity to Renal Cancer A498. Concerning the antimycobacterial activity, only the hybrid compound, 9, has a significant activity. SAR correlations have been performed.

Aim: Over the last decades, few significant achievements have been made in tuberculosis (TB) therapy. As a result, there is an urgent need for new anti-TB drugs. Results: Two new classes of bis-(im...

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.

In this study a straightforward and efficient approach concerning synthesis of 1,3-diazole derivatives under ultrasound (US) irradiation as well as under conventional thermal heating (TH) is presented. N-alkylation under US irradiation may be considered environmentally friendly in terms of higher yields, smaller amounts of solvent used and an overall energy efficiency due to a substantial reduction of reaction times. A comparative study of ultrasound vs. conventional conditions has been performed. Overall, the use of US proved to be more efficient than TH. A possible explanation concerning the different behavior of imidazole and benzimidazole in the N1-alkylation reactions under US irradiation was proposed.