Pharmacophore Modelling of Vanillin Derivatives, Favipiravir, Chloroquine, Hydroxychloroquine, Monolaurin and Tetrodotoxin as MPro inhibitors of Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2)

Ligand-based pharmacophore modelling approach using four established antiviral drugs, namely remdesivir, lopinavir, ritonavir and hydroxychloroquine were analysed for COVID-19 inhibitors as training sets. Twenty vanillin derivatives together with monolaurin were used as test sets to evaluate potential as SARS-CoV-2 inhibitors. Structure-based pharmacophore modelling approach was also performed using Protein Data Bank information: PDB-5RE6, 5REX and 5RFZ in order to analyse the binding site and ligand-protein complex interactions. The pharmacophore modelling mode of 5RE6 displayed two Hydrogen Bond Acceptors (HBA) and one Hydrophobic (HY) interaction. Besides, the pharmacophore model of 5REX showed two HBA and two HY interactions. Finally, the pharmacophore model of 5RFZ showed three HBA and one HY interaction. Based on ligand-based approach, 20 Schiff-based vanillin derivatives, namely vanillin associated with methyl-6- aminopyridine-3-carboxylate (1), sepiapterin (2), 6-aminopyridine-3-carboxylic acid (3), 6-aminopyridine-2-carboxylic acid (4), pemoline (5), α-phenylglycine (6), 2-amino-4-hydroxy-3-methylpentanoic acid (7), 4-hydroxyphenylglycine (8), β-homoserine (9), allylglycine (10), oxamic acid (11) benzophenone hydrazine (12), 2-aminoadipic acid (13), D-alanyl-D-alanine (14), p-bromophenylalanine (15), nicotinic hydrazide (16), 4-hydroxybenzhydrazide (17), benzohydrazide (18), isonicotinic hydrazide (19), and phenylhydrazine (20) showed strong MPro inhibition activity. This was due to their good alignment and common features to PDB-5RE6. Similarly, monolaurin and tetrodotoxin displayed some significant activity against SARS-CoV-2. From structure-based approach, vanillin derivatives (1) to (12) displayed some potent MPro inhibition against SARS-CoV-2. Favipiravir, chloroquine and hydroxychloroquine also showed some significant MPro inhibition. Favipiravir showed good alignment and common pharmacophore features to PDB- 5RFZ, whereas chloroquine and hydroxychloroquine showed good alignment and common pharmacophore features to PDB-5REX.

Detection of Al3+ and Cu2+ ions by isonicotinohydrazide based chemosensors and its application to live cell imaging.

A new Schiff base receptor (3) was synthesized by an equimolar reaction between the isonicotinic hydrazide and 2,4-dihydroxybenzaldehyde in ethanol. Receptor 3 based demonstrated excellent selectivity and sensitivity towards Cu2+...

Solid State Analysis and Theoretical Explorations on Polymorphic and Hydrate Forms of p-Hydroxybenzaldehyde Isonicotinichydrazone: Effect of Additives on Polymorphic Crystallization

The reaction of p-hydroxybenzaldehyde with an equimolar amount of isonicotinic hydrazide afforded two polymorphic and hydrate forms of p-hydroxybenzaldehyde isonicotinichydrazone (HBIH) by varying the experimental reaction conditions. The compounds are fully characterized by means of single crystal and powder diffraction methods, vibrational spectroscopy (FT-IR and Raman), thermal and elemental analysis. The compound crystallizes in three different forms in two different space groups, P21/c (form PA and PB) and Pbca (PC). The Hirshfeld surface analysis shows the differences in the relative contributions of intermolecular interactions to the total Hirshfeld surface area for the HBIH molecules. The calculated pairwise interaction energies (104-116 kJ/mol) can be related to the stability of the crystals. Energy framework analysis identifies the interaction hierarchy and their topology. The geometry and conformation of the three forms are essentially similar which differ only by packing arrangement.

Solid State Analysis and Theoretical Explorations on Polymorphic and Hydrate Forms of p-Hydroxybenzaldehyde Isonicotinichydrazone: Effect of Additives on Polymorphic Crystallization

The reaction of p-hydroxybenzaldehyde with an equimolar amount of isonicotinic hydrazide afforded two polymorphic and hydrate forms of p-hydroxybenzaldehyde isonicotinichydrazone (HBIH) by varying the experimental reaction conditions. The compounds are fully characterized by means of single crystal and powder diffraction methods, vibrational spectroscopy (FT-IR and Raman), thermal and elemental analysis. The compound crystallizes in three different forms in two different space groups, P21/c (form PA and PB) and Pbca (PC). The Hirshfeld surface analysis shows the differences in the relative contributions of intermolecular interactions to the total Hirshfeld surface area for the HBIH molecules. The calculated pairwise interaction energies (104-116 kJ/mol) can be related to the stability of the crystals. Energy framework analysis identifies the interaction hierarchy and their topology. The geometry and conformation of the three forms are essentially similar which differ only by packing arrangement.