Benzoquinoline Derivatives: A Straightforward and Efficient Route to Antibacterial and Antifungal Agents

• Main Authors: Vasilichia Antoci (Author), Liliana Oniciuc (Author), Dorina Amariucai-Mantu (Author), Costel Moldoveanu (Author), Violeta Mangalagiu (Author), Andreea Madalina Amarandei (Author), Claudiu N. Lungu (Author), Simona Dunca (Author), Ionel I. Mangalagiu (Author), Gheorghita Zbancioc (Author)
• Format: Book
• Published: MDPI AG, 2021-04-01T00:00:00Z.
• Subjects: article
• Online Access: Connect to this object online.

Summary

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 (<b>BQS</b>) and pyrrolobenzo[f]quinolinium cycloadducts (<b>PBQC</b>)-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 <b>BQS</b> salts have an excellent quasi-nonselective antifungal activity against the fungus <i>Candida albicans</i> (some of them higher that the control drug nystatin) and very good antibacterial activity against the Gram positive bacterium <i>Staphylococcus aureus</i>. The <b>PBQC</b> 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 <b>BQS</b> salts. Studies of the interaction of each <b>BQS</b> salt <b>3a-o</b> with ATP synthase in the formed complex, reveal that salts <b>3j</b>, <b>3i,</b> and <b>3n</b> have the best fit in a complex with ATP synthase. Study of the interaction of each <b>BQS</b> salt <b>3a-o</b> with TOPO II in the formed complex reveals that salts <b>3j</b> and <b>3n</b> have the best-fit in complex with TOPO II. The in silico ADMET studies reveal that the <b>BQS</b> salts have excellent drug-like properties, including a low toxicity profile. Overall, the experimental and in silico studies indicate that compounds <b>3e</b> and <b>3f</b> (from the aliphatic series), respectively, and <b>3i</b>, <b>3j</b> and <b>3n</b> (from the aromatic series), are promising leading drug candidates.

Item Description

10.3390/ph14040335
1424-8247