Synthesis of Sporidesmin Based Antigens

<p>In a program aimed at developing a chemically derived vaccine against sporidesmin-A, the toxin which causes the pasture disease facial eczema, two haptens have been prepared, coupled to protein carriers, and tested for immunogenicity. The hapten, 2-amino-5-chloro-3,4-dimethoxybenzyl alcohol has been synthesised from vanillin and the general synthetic methods developed in the course of this work have been used to prepare a large number of related vanillin derivatives for use in cross-hapten studies. The carbon-13 nuclear magnetic resonance spectra of 16 vanillin derivatives have been obtained, and two independent methods of deducing vanillin substitution patterns have been developed. 5-chloro-6, 7-dimethoxy-N-methyl-lH-indole has been prepared by a new route and its 3-oxoacetic acid derivative has been synthesized for use as a hapten. The Vilsmeier-Haack intermediate, l-methyl-3-(N,N-dimethylimonio) methyl-lH-indole chloride was isolated and a number of possible synthetic routes from it to pyrroloindoles were explored. The vanillin and indole haptens have been coupled to protein carriers to form antigens which generated a low antibody response. However, the use of mycobacterium phlei as a carrier greatly increased the antibody response but the antibodies produced did not interact strongly with sporidesmin-A.</p>

Synthesis of Sporidesmin Based Antigens

<p>In a program aimed at developing a chemically derived vaccine against sporidesmin-A, the toxin which causes the pasture disease facial eczema, two haptens have been prepared, coupled to protein carriers, and tested for immunogenicity. The hapten, 2-amino-5-chloro-3,4-dimethoxybenzyl alcohol has been synthesised from vanillin and the general synthetic methods developed in the course of this work have been used to prepare a large number of related vanillin derivatives for use in cross-hapten studies. The carbon-13 nuclear magnetic resonance spectra of 16 vanillin derivatives have been obtained, and two independent methods of deducing vanillin substitution patterns have been developed. 5-chloro-6, 7-dimethoxy-N-methyl-lH-indole has been prepared by a new route and its 3-oxoacetic acid derivative has been synthesized for use as a hapten. The Vilsmeier-Haack intermediate, l-methyl-3-(N,N-dimethylimonio) methyl-lH-indole chloride was isolated and a number of possible synthetic routes from it to pyrroloindoles were explored. The vanillin and indole haptens have been coupled to protein carriers to form antigens which generated a low antibody response. However, the use of mycobacterium phlei as a carrier greatly increased the antibody response but the antibodies produced did not interact strongly with sporidesmin-A.</p>

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.

Influence of Vanillin Acrylate-Based Resin Composition on Resin Photocuring Kinetics and Antimicrobial Properties of the Resulting Polymers

The investigation of the influence of vanillin acrylate-based resin composition on photocuring kinetics and antimicrobial properties of the resulting polymers was performed in order to find efficient photocurable systems for optical 3D printing of bio-based polymers with tunable rigidity, as well as with antibacterial and antifungal activity. Two vanillin derivatives, vanillin diacrylate and vanillin dimethacrylate, were tested in photocurable systems using phenyl bis(2,4,6-trimethylbenzoyl)phosphine oxide as a photoinitiator. The influence of vanillin acrylate monomer, amount of photoinitiator, presence and amount of dithiol, and presence of solvent on photocuring kinetics was investigated by real-time photoreometry. Polymers of different rigidity were obtained by changing the photocurable resin composition. The photocuring kinetics of the selected vanillin acrylate-based resins was comparable with that of commercial petroleum-based acrylate resins for optical 3D printing. Polymers based on both vanillin acrylates showed a significant antibacterial activity against Escherichia coli and Staphylococcus aureus. Vanillin diacrylate-based polymer films also demonstrated an antifungal activity in direct contact with Aspergillus niger and Aspergillus terreus. Vanillin diacrylate-based dual curing systems were selected as the most promising for optical 3D printing of bio-based polymers with antibacterial and antifungal activity.

Pharmacophore modelling of vanillin derivatives, favipiravir, chloroquine, hydroxychloroquine, monolaurin and tetrodotoxin as MPro inhibitors of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2)

Objectives The aim of this study was to use Ligand-based pharmacophore modelling approach for four established antiviral drugs, namely remdesivir, lopinavir, ritonavir and hydroxychloroquine for COVID-19 inhibitors as training sets. In this study Twenty vanillin derivatives together with monolaurin and tetrodotoxin were used as test sets to evaluate as potential SARS-CoV-2 inhibitors. The Structure-based pharmacophore modelling approach was also performed using 5RE6, 5REX and 5RFZ in order to analyse the binding site and ligand–protein complex interactions. Results 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, 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.