Isatin based macrocyclic Schiff base ligands as novel candidates for antimicrobial and antioxidant drug design: In vitro DNA binding and biological studies

• Published in: Journal of photochemistry and photobiology. B, Biology Vol. 183; pp. 191 - 200
• Main Authors: Bharathi Dileepan, A.G., Daniel Prakash, T., Ganesh Kumar, A., Shameela Rajam, P., Violet Dhayabaran, V., Rajaram, R.
• Format: Journal Article
• Language: English
• Published: Switzerland Elsevier B.V 01-06-2018; Elsevier BV
• Subjects: Antiinfectives and antibacterials; Antimicrobial activity; Antioxidants; Atoms & subatomic particles; Bacteria; Binding; Circular dichroism; Deoxyribonucleic acid; Dichroism; DNA; DNA binding studies; Drug development; Fluorescence; Imines; Infrared radiation; Ionization; Isatin; Ligands; Macrocyclic compounds; Macrocyclic Schiff base; Membrane proteins; Molecular docking; Nitrogen; NMR; Nuclear magnetic resonance; Proteins; Spectral analysis; Spectral characterization; Spectroscopy; Two dimensional analysis; Viscosity; Macrocyclic Schiff base; DNA binding studies; Antimicrobial activity; Spectral characterization; Isatin; Molecular docking
• ISSN: 1011-1344; 1873-2682
• DOI: 10.1016/j.jphotobiol.2018.04.029

In the present work, five macrocyclic compounds, C18H12N2O4 (1), C38H24N8O6 (1a), C38H24N8O4S2 (1b), C40H32N8O4 (2a) and C48H32N8O4 (2b) have been synthesized and thoroughly characterized by elemental analysis, FT-IR, 1D & 2D NMR and electron spray ionization mass spectral analysis. The DNA binding ability of these compounds were investigated in vitro by UV–Visible, fluorescence, circular dichroism (CD) spectroscopy and viscosity measurements. The results indicate that these compounds possess strong DNA binding affinity via intercalation, while the order of binding strength followed the trend 2b (1.52 ± 0.06 × 105 M−1) > 2a (1.12 ± 0.11 × 105 M−1) > 1b (1.05 ± 0.04 × 105 M−1) > 1a (0.97 ± 0.14 × 104 M−1) > 1 (0.75 ± 0.21 × 104 M−1). The radical scavenging potencies of the compounds were explored by employing DPPH, OH and NO assays, in which 1a exhibited highest inhibitory effect on the radicals (IC50 = 23.59 μM (DPPH), 26.14 μM (OH), 28.41 μM (NO)). The in vitro antibacterial studies showed that these compounds have the potential to arrest the growth of bacteria, among which, 1a was found to be vulnerable against the bacterial stains. In addition, in silico molecular docking stimulations were also performed to position these compounds into the active sites of bacterial membrane proteins. The results of in vitro and in silico investigations reveal that the compounds apprehend the bacterial growth significantly. The data obtained from this piece of work would be helpful to design antibacterial drugs incorporating isatin based macrocyclic frameworks.
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•Synthesis and structural characterizations of a series of isatin based macrocyclic Schiff base ligands.•All the compounds bind to DNA via Intercalation•Significant scavenging ability towards DPPH, OH radical than NO radical.•In vitro and in silico investigations on antibacterial potential of the compounds.•The compounds apprehend the bacterial growth significantly.