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Objective(s): Biofilm-associated infections are challenging to manage or treat since the biofilm matrix is impenetrable to most antibiotics. Therefore, the best approach to deal with biofilm infections is to interrupt the construction during the initial levels. Biofilm formation has been regulated through the quorum sensing (QS) network, making it an attractive target for any antibacterial therapy. Materials and Methods: Here, some coumarin members, including umbelliprenin, 4-farnesyloxycoumarin, gummosin, samarcandin, farnesifrol A, B, C, and auraptan, have been assessed as QS inhibitors in silico and in vitro. Their potential inhibitory effects on biofilm formation and virulence factor production of Pseudomonas aeruginosa PAO1 were evaluated. Results: First, the interaction of these compounds was investigated against one of the major transcriptional regulator proteins, PqsR, using molecular docking and structural analysis methodology. After that, in vitro evaluations indicated that 4-farnesyloxycoumarin and farnesifrol B showed considerable reduction in biofilm formation (62% and 56%, respectively), virulence factor production, and synergistic effects with tobramycin. Moreover, 4-farnesyloxycoumarin significantly (99.5%) reduced PqsR gene expression. Conclusion: The biofilm formation test, virulence factors production assays, gene expression analysis, and molecular dynamic simulations data demonstrated that coumarin derivatives are a potential antiQS family through PqsR inhibition. [ABSTRACT FROM AUTHOR]

Objective: The present study was conducted to find cytotoxic compounds from oleo-gum-resin of Ferula assa-foetida (asafoetida). Materials and Methods: A dichloromethane extract of asafoetida was subjected to different chromatography analyses (including column chromatography, preparative thin layer chromatography and high performance liquid chromatography) to isolate its bioactive sesquiterpene coumarins. The structures of isolated compounds were elucidated through 1H-NMR spectra interpretation and comparison with those reported in the literature. To measure the cytotoxic activity of pure compounds, a non-fluorescent substrate called resazurin (alamarBlue®) was used in this study. Human breast and prostate cancer cell lines (MCF-7 and PC-3, respectively) and a normal human embryonic stem cell (NIH) were treated with different concentrations (50, 25, 12.5 and 6.25 µg/mL) of pure compounds. Results: In this study, 10 sesquiterpene coumarins were isolated from oleo-gum-resin of F. assa-foetida and cytotoxic activity of 6 compounds was tested against MCF-7 and PC-3 cell lines and NIH cells. Badrakemin acetate (7), ferukrinone (8) and deacetyl kellerin (10) were found for the first time in the oleo-gum-resin of F. assafoetida. Gummosin (4) showed moderate cytotoxic activity with IC50 values of 30 and 32.1 µg/mL against PC-3 and MCF-7 cell lines, respectively. None of the isolated compounds showed toxicity against NIH as a normal human cell line. Conclusion: The preferential cytotoxic activity of gummosin against cancer cell lines is reported for the first time in this study. [ABSTRACT FROM AUTHOR]