N-alkylimidazole derivatives as potential inhibitors of quorum sensing in Pseudomonas aeruginosa.

Antimicrobial resistance is a threat to global public health. Microbial resistance is mediated by biofilm formation and virulence behavior during infection. Quorum sensing (QS), a cell-to-cell communication is frequently used by microbes to evade host immune systems. Inhibiting QS channels is a potential route to halt microbial activities and eliminate them. Imidazole has been shown to be a potent warhead in various antimicrobial agents. This study aims to evaluate alkyl-imidazole derivatives as potential inhibitors of QS and to explore the interactions of the compounds with LasR, a key protein in the QS machinery of Pseudomonas aeruginosa. The study revealed that imidazole derivatives with longer alkyl chains possessed better antimicrobial activities. Octylimidazole and decylimidazole emerged as compounds with better anti-virulence and biofilm inhibition properties while hexylimidazole showed the best inhibitory activity against Pseudomonas aeruginosa PAO1. The binding affinity of the compounds with LasR followed a similar trend as that observed in the QS inhibitory assays, suggesting that interaction with LasR may be important for QS inhibition.

In Vivo Antiplasmodial Activity and Toxicological Analyses of the Ethanolic Leaf and Twig Extract of Faurea speciosa Welw. (Proteaceae).

In Africa, medicinal plants are commonly used to treat malaria and other diseased conditions. The ethanolic leaf and twig extract of Faurea speciosa has been shown to possess promising antiplasmodial properties. This present study was aimed at investigating its antiplasmodial effect in vivo. Qualitative phytochemical screening was carried out on the plant samples using standard methods. The antiplasmodial effect against early infection, curative effect against established infection, and prophylactic effect against residual infection were studied in vivo in Plasmodium berghei-infected mice while the carrageenan-induced edema model in chicks was used for anti-inflammatory tests. The phosphomolybdenum and DPPH radical scavenging assays were used in the evaluation of antioxidant potential. Acute toxicity of the extract was evaluated using the Organization for Economic Cooperation and Development (OECD) guidelines. Phytochemical screening of plant samples revealed the presence of flavonoids, coumarins, tannins, saponins, and glycosides. Faurea speciosa leaf and twig extract exhibited significant antiplasmodial activities in the mouse model with parasite suppression rates of 66.63%, 71.70%, and 56.93% in the suppressive, curative, and prophylactic tests, respectively. A 55.50% reduction of edema in the anti-inflammatory test indicated moderate success in reducing inflammation. The total antioxidant capacity of the extract was determined to be 65.4 mg AAE/g of extract, while in the DPPH radical scavenging assay, the IC50 value was found to be 499.4 µg/mL. With the exception of an inconsistent rise in urea level, there was no significant difference in the other biochemistry parameters in the acute toxicity studied. The median lethal dose (LD50) of the extract was over 2000 mg/kg. The results of this study show that Faurea speciosa leaf and twig extract has promising antimalarial capabilities and is fairly safe at low concentrations.

Alkaloids from Cryptolepis sanguinolenta as Potential Inhibitors of SARS-CoV-2 Viral Proteins: An In Silico Study.

The ongoing global pandemic caused by the human coronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has infected millions of people and claimed hundreds of thousands of lives. The absence of approved therapeutics to combat this disease threatens the health of all persons on earth and could cause catastrophic damage to society. New drugs are therefore urgently required to bring relief to people everywhere. In addition to repurposing existing drugs, natural products provide an interesting alternative due to their widespread use in all cultures of the world. In this study, alkaloids from Cryptolepis sanguinolenta have been investigated for their ability to inhibit two of the main proteins in SARS-CoV-2, the main protease and the RNA-dependent RNA polymerase, using in silico methods. Molecular docking was used to assess binding potential of the alkaloids to the viral proteins whereas molecular dynamics was used to evaluate stability of the binding event. The results of the study indicate that all 13 alkaloids bind strongly to the main protease and RNA-dependent RNA polymerase with binding energies ranging from -6.7 to -10.6 kcal/mol. In particular, cryptomisrine, cryptospirolepine, cryptoquindoline, and biscryptolepine exhibited very strong inhibitory potential towards both proteins. Results from the molecular dynamics study revealed that a stable protein-ligand complex is formed upon binding. Alkaloids from Cryptolepis sanguinolenta therefore represent a promising class of compounds that could serve as lead compounds in the search for a cure for the corona virus disease.