Antioxidant and Antimicrobial Potential of 1,8‐Naphthyridine Based Scaffolds: Design, Synthesis and in Silico Simulation Studies within Topoisomerase II

• Published in: Chemistry & biodiversity Vol. 21; no. 6; pp. e202301746 - n/a
• Main Authors: Elkanzi, Nadia A. A., Hrichi, Hajer, Muqbil Alsirhani, Alaa, Bakr, Rania B.
• Format: Journal Article
• Language: English
• Published: Switzerland Wiley Subscription Services, Inc 01-06-2024
• Subjects: 1,8-naphthyridine; Anti-Bacterial Agents - chemical synthesis; Anti-Bacterial Agents - chemistry; Anti-Bacterial Agents - pharmacology; Antifungal activity; Antifungal Agents - chemical synthesis; Antifungal Agents - chemistry; Antifungal Agents - pharmacology; Antiinfectives and antibacterials; antimicrobial; Antimicrobial activity; Antimicrobial agents; antioxidant; Antioxidants; Antioxidants - chemical synthesis; Antioxidants - chemistry; Antioxidants - pharmacology; Ascorbic acid; Bacteria - drug effects; beta-Lactams - chemical synthesis; beta-Lactams - chemistry; beta-Lactams - pharmacology; Biphenyl Compounds - antagonists & inhibitors; Chemical analysis; DNA topoisomerase (ATP-hydrolysing); DNA Topoisomerases, Type II - metabolism; Drug Design; Free radicals; Fungi - drug effects; Fungicides; Mass spectra; Microbial Sensitivity Tests; Molecular docking; Molecular Docking Simulation; Molecular Structure; Naphthyridines - chemical synthesis; Naphthyridines - chemistry; Naphthyridines - pharmacology; NMR; Nuclear magnetic resonance; Picrates - antagonists & inhibitors; Scavenging; Spiro Compounds - chemical synthesis; Spiro Compounds - chemistry; Spiro Compounds - pharmacology; spiro β-Lactam; Structure-Activity Relationship; Synthesis; thiazolidinone; Topoisomerase II Inhibitors - chemical synthesis; Topoisomerase II Inhibitors - chemistry; Topoisomerase II Inhibitors - pharmacology; spiro β-Lactam; antimicrobial; 1,8-naphthyridine; antioxidant; thiazolidinone
• ISSN: 1612-1872; 1612-1880; 1612-1880
• DOI: 10.1002/cbdv.202301746

A series of spiro β‐Lactams (4 a–c, 7 a–c) and thiazolidinones (5 a–c, 8 a–c) possessing 1,8‐naphthyridine moiety were synthesized in this study. The structure of the newly synthesized compounds has been confirmed by IR, 1H‐NMR, 13C NMR, mass spectra, and elemental analysis. The synthesized compounds were tested in vitro for their antibacterial and antifungal activity against various strains. The antimicrobial data showed that most of the compounds displayed good efficacy against both bacteria and fungi. The structure‐activity relationship (SAR) studies suggested that the presence of electron‐withdrawing chloro (3 b, 4 b, and 5 b) and nitro groups (7 b, 8 b) at the para position of the phenyl ring improved the antimicrobial activity of the compounds. The free radical scavenging assay showed that all the synthesized compounds exhibited significant antioxidant activity on DPPH. Compounds 8 b (IC50=17.68±0.76 μg/mL) and 4 c (IC50=18.53±0.52 μg/mL) showed the highest antioxidant activity compared to ascorbic acid (IC50=15.16±0.43 μg/mL). Molecular docking studies were also conducted to support the antimicrobial and SAR results.