Ligand based pharmacophoric modelling and docking of bioactive pyrazolium 3-nitrophthalate (P3NP) on Bacillus subtilis, Aspergillus fumigatus and Aspergillus niger — Computational and Hirshfeld surface analysis

• Published in: Journal of photochemistry and photobiology. B, Biology Vol. 163; pp. 352 - 365
• Main Authors: Balachandar, S., Sethuram, M., Muthuraja, P., Shanmugavadivu, T., Dhandapani, M.
• Format: Journal Article
• Language: English
• Published: Switzerland Elsevier B.V 01-10-2016
• Subjects: Absorption, Physicochemical; Animals; Anti-Infective Agents - metabolism; Anti-Infective Agents - pharmacokinetics; Anti-Infective Agents - pharmacology; Anti-Infective Agents - toxicity; Antimicrobial; Aspergillus fumigatus - drug effects; Aspergillus niger - drug effects; Bacillus subtilis - drug effects; DFT; Dogs; Hirshfeld surface analysis; Humans; Hydrogen Bonding; Ligands; Madin Darby Canine Kidney Cells; MIC; Models, Molecular; Molecular Conformation; Molecular docking; Pharmacophore; Phthalic Acids - metabolism; Phthalic Acids - pharmacokinetics; Phthalic Acids - pharmacology; Phthalic Acids - toxicity; Pyrazoles - metabolism; Pyrazoles - pharmacokinetics; Pyrazoles - pharmacology; Pyrazoles - toxicity; Quantum Theory; Static Electricity; Antimicrobial; Hirshfeld surface analysis; DFT; Pharmacophore; MIC; Molecular docking
• ISSN: 1011-1344; 1873-2682
• DOI: 10.1016/j.jphotobiol.2016.08.045

Biologically active Lewis acid-base compound, pyrazolium 3-nitro phthalate (P3NP) has been synthesized and crystallized by slow evaporation - solution method at 30°C. Spectral and single crystal X-Ray diffraction (XRD) were used to characterize the compound. The stability of the P3NP was confirmed by UV–Visible spectral analysis. P3NP crystallizes in monoclinic P21/C space group with cell parameters, a=13.009 (3) Å, b=12.584 (3) Å, c=7.529 (18) Å and β=93.052 (4)o with Z=4. Crystal packing was stabilized by N+H⋯O−, OH⋯O and CH⋯O intermolecular hydrogen bonds. The nature of anion - cation interactions and crystal packing from various types of intermolecular contacts and their importance were explored using the Hirshfeld surface analysis. The structure was optimized by Density Functional Theory at B3LYP level with 6-311++G(d,p) basis set and the vibrational frequencies were theoretically calculated. Band gap between Highest Occupied Molecular Orbital (HOMO) and Lowest Unoccupied Molecular Orbital (LUMO) and Electrostatic potential (ESP) were calculated. Antimicrobial activities of P3NP with targets were clinically tested and were found to exhibit antibacterial activity against gram positive and antifungal activity against pathogens with Minimum Inhibitory Concentration (MIC). Ligand based pharmacophore modelling was used to understand the potential of P3NP ligand to bind with selected target proteins. iGEM Dock was used to predict the modes of interactions of the ligand with target proteins of the microbes predicted from pharmacophore. PreADMET predicts no absorption of ligand in Human Intestinal Absorption (HIA).
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•Pharmacological action of P3NP ligand evaluated on selected microbes•Active sites of P3NP predicted through Ligand Scout software•ESP reveals active nucleophilic and electrophilic sites of ligand.•Hirshfeld surface analysis validates all type of interactions during docking.•PreADMET predicts appreciable results in Human Intestinal Absorption (HIA).