Synthesis, Photophysical Characterization and Evaluation of Biological Properties of C7, a Novel Symmetric Tetra-Imidazolium-Bis-Heterocycle.

A novel symmetric tetra-imidazolium-bis-heterocycle, called C7, was designed and synthesized in a quick two-step pathway, with the objective to synthesize biologically active supramolecular assembly. The synthesized compound was then analyzed for its photophysical properties, for a potential application in theragnostic (fluorescence) or phototherapy (photodynamic therapy, with the production of reactive oxygen species, such as singlet oxygen 1O2). C7 was thus screened for its biological activity, in particular against important human pathogens of viral origin (respiratory viruses such as adenovirus type 2 and human coronavirus 229E) and of fungal and bacterial origin. The compound showed limited antiviral activity, combined with very good antiproliferative activity against breast cancer, and head and neck squamous cell carcinoma models. Interestingly, the selected compound showed excellent antibacterial activity against a large array of Gram-positive and Gram-negative clinically isolated pathogenic bacteria, with a possible inhibitory mechanism on the bacterial cell wall synthesis studied with electron microscopy and molecular docking tools. Collectively, the newly synthesized compound C7 could be considered as a potential lead for the development of new antibacterial treatment, endowed with basic photophysical properties, opening the door towards the future development of phototherapy approaches.

In silico evidence of antiviral activity against SARS-CoV-2 main protease of oligosaccharides from Porphyridium sp.

The coronavirus pandemic (COVID-19) has created an urgent need to develop effective strategies for prevention and treatment. In this context, therapies against protease Mpro, a conserved viral target, would be essential to contain the spread of the virus and reduce mortality. Using combined techniques of structure modelling, in silico docking and pharmacokinetics prediction, many compounds from algae were tested for their ability to inhibit the SARS-CoV-2 main protease and compared to the recent recognized drug Paxlovid. The screening of 27 algal molecules including 15 oligosaccharides derived from sulfated and non-sulphated polysaccharides, eight pigments and four poly unsaturated fatty acids showed high affinities to interact with the protein active site. Best candidates showing high docking scores in comparison with the reference molecule were sulfated tri-, tetra- and penta-saccharides from Porphyridium sp. exopolysaccharides (SEP). Structural and energetic analyses over 100 ns MD simulation demonstrated high SEP fragments-Mpro complex stability. Pharmacokinetics predictions revealed the prospects of the identified molecules as potential drug candidates.

Apigenin analogues as SARS-CoV-2 main protease inhibitors: In-silico screening approach.

The COVID-19 new variants spread rapidly all over the world, and until now scientists strive to find virus-specific antivirals for its treatment. The main protease of SARS-CoV-2 (Mpro) exhibits high structural and sequence homology to main protease of SARS-CoV (93.23% sequence identity), and their sequence alignment indicated 12 mutated/variant residues. The sequence alignment of SARS-CoV-2 main protease led to identification of only one mutated/variant residue with no significant role in its enzymatic process. Therefore, Mpro was considered as a high-profile drug target in anti-SARS-CoV-2 drug discovery. Apigenin analogues to COVID-19 main protease binding were evaluated. The detailed interactions between the analogues of Apigenin and SARS-CoV-2 Mpro inhibitors were determined as hydrogen bonds, electronic bonds and hydrophobic interactions. The binding energies obtained from the molecular docking of Mpro with Boceprevir, Apigenin, Apigenin 7-glucoside-4'-p-coumarate, Apigenin 7-glucoside-4'-trans-caffeate and Apigenin 7-O-beta-d-glucoside (Cosmosiin) were found to be -6.6, -7.2, -8.8, -8.7 and -8.0 kcal/mol, respectively. Pharmacokinetic parameters and toxicological characteristics obtained by computational techniques and Virtual ADME studies of the Apigenin analogues confirmed that the Apigenin 7-glucoside-4'-p-coumarate is the best candidate for SARS-CoV-2 Mpro inhibition.