Quorum sensing (QS) is a system used in the expression of virulence factors by many pathogenic bacteria, and blockage of the system is seen as a new and effective strategy in combating with resistant bacteria. The inhibition effects of two benzimidazolium salts, namely 1-(2-methylbenzonitrile)-3-benzylbenzimidazolium bromide (2) and 1-(N-methylphthalimide)-3-(4-methylbenzyl)benzimidazolium bromide (3), on quorum sensing-related virulence factors such as pyocyanin, elastase, biofilm formation and swarming motility, which is an opportunistic pathogen Pseudomonas aeruginosa PA01, were investigated in this study. The results show that the compound 3 has a significant inhibition on biofilm formation with 94%. Furthermore, the compounds 2 and 3 reduced swarming motility by 64–69% as well as pyocyanin production by 49–64% in P. aeruginosa PA01 without preventing bacterial growth in the tested concentrations. HF, B3LYP and M06–2X methods were used with 3–21 g, 6–31 g, sdd basis sets to compare the chemical activity of the compounds. Theoretically, ¹H NMR, ¹³C NMR and Infrared spectra of the compounds were calculated in the HF/6-31++g basis set. The biological activities of the relative compounds were theoretically studied against cancer proteins. Crystal structure of the BRCT repeat region from the breast cancer associated protein, ID: 1JNX, crystal structure of liver cancer protein, ID: 3WZE and crystal structure of lung cancer protein, ID: 5ZMA, were compared. In the docking studies, the best result was obtained with compound 2 against the lung cancer cell with a docking score parameter of −5.85. Communicated by Ramaswamy H. Sarma Graphical Abstract

The aim of this study is to investigate the phytochemical contents and antibacterial properties of 2-year Prunus avium L. standard cultivars [Cristalina (Cr), 0900 Ziraat (Zr)] and to elucidate the mechanism of action of the extracts on the quorum sensing (QS) system by using homology modelling and molecular docking. Phenolic contents of methanol extract of Cr and Zr stalks were detected by HPLC. As a result, catechin hydrate (6364·67–8127·93 µg g⁻¹) and chlorogenic acid (998·81–1273·4 µg g⁻¹) were found to be the highest in stalk extracts in the two varieties in 2017. All extracts had inhibitory effect on Gram-positive bacteria. Stalk extract of Zr showed higher inhibition rate (86%) on swarming motility. Stalk samples of Zr collected in 2017 and 2018 also reduced biofilm formation by 75 and 73%, respectively. The computational analysis revealed that one of the major component of the extracts, chlorogenic acid, was able to bind to the QS system receptors, LasR, RhlR, and PqsR. Therefore, the mechanism of decreasing the production of virulence factors by the extracts might be through inhibiting these receptors and thus interfering with the QS system.

The emergence of bacteria resistant to conventional antibiotics and the inability of these antibiotics to treat bacterial biofilm-induced infections cause millions of deaths every year. This situation has prompted scientists to develop alternative strategies to combat infectious diseases. Among these, researches on phytochemicals to reduce bacterial virulence in Pseudomonas aeruginosa have gained momentum in recent years. The main reasons behind this are the production of virulence factors and biofilm formation, all of which are under the control of quorum sensing (QS) system. Hence, inhibition of the QS pathways is an eligible strategy for the control of microbial pathogenesis. For the first time in the present study, the methanolic seed extract of avocado was evaluated for its anti-QS activity against P. aeruginosa PAO1. The results of the experiments carried out proved that the extract has inhibitory activity on the regulation of virulence and biofilm formation. Phytochemical analysis resulted in the identification of epicatechin, catechin, chlorogenic acid, caffeic acid, quercetin, kaempferol, vanillin, ferulic acid in the extract. Then, the mechanism of action for the extract was investigated through molecular docking. Docking outcomes demonstrated that the major components, catechin, epicatechin, chlorogenic acid, could bind to the receptors of QS competitively. Hence, the mode of action for the extract might be through the inhibition of the QS. Considering the computational analysis results and the literature, it is thought that the anti-QS activity of the extract prepared from avocado seeds may be related to the synergistic effect of the phytochemicals it contains.