Antipathogenic drugs are a potential source of therapeutics, particularly following the emergence of multiple drug-resistant pathogenic microorganisms in the last decade. The inhibition of quorum sensing (QS) is an advanced antipathogenic approach for suppression of bacterial virulence and dissemination. This study aimed to investigate the inhibitory effect of some Egyptian medicinal plants on the QS signaling system of Pseudomonas aeruginosa. Among the tested plants, Mangifera indica exhibited the highest quorum sensing inhibition (QSI) activity against Chromobacterium violaceum ATCC 12472. Four pure compounds were extracted and identified; of these, methyl gallate (MG) showed the most potent QSI. MG had a minimum inhibitory concentration (MIC) of 512 g/mL against P. aeruginosa strains PAO1, PA14, Pa21, Pa22, Pa23, Pa24, and PAO-JP2. The virulence factors of PAO1, PA14, Pa21, Pa22, Pa23, and Pa24 were significantly inhibited by MG at 1/4 and 1/2 sub-MICs without affecting bacterial viability. Computational insights were performed by docking the MG compound on the LasR receptor, and the QSI behavior of MG was found to be mediated by three hydrogen bonds: Trp60, Arg61, and Thr75. This study indicates the importance of M. indica and MG in the inhibition and modulation of QS and QS-related virulence factors in P. aeruginosa.

Some fluoroquinazolinones (A–H) were designed, synthesized and biologically evaluated for their antitumor activity against the two cell lines, MCF-7 and MDA-MBA-231. New derivative G (IC₅₀ = 0.44 ± 0.01 µM) showed antitumor activity, better than that of the reference drug erlotinib (IC₅₀ = 1.14 ± 0.04 µM) against MCF-7. New derivative E (IC₅₀ = 0.43 ± 0.02 µM) showed higher activity than the reference drug erlotinib (IC₅₀ = 2.55 ± 0.19 µM) against MDA-MBA-231. Furthermore, the EGFR (epidermal growth factor receptor) and tubulin inhibition assays were carried out for the highest active derivatives to reveal the expected mechanism of action. They exhibited significant results compared to the reference drugs. Molecular docking simulations were performed on EGFR and tubulin binding sites to rationalize the experimental results and describe their binding modes. The results of the molecular modeling study were correlated with that of the antitumor screening.

A series of new fluoroquinazolinone 6–8 and 10a–g derivatives was designed, prepared and screened for their in vitro cytotoxic activity against human cancer cell lines MCF-7 and MDA-MBA-231. Compounds 6 (IC₅₀ = 0.35 ± 0.01 µM), 10f (IC₅₀ = 0.71 ± 0.01 µM), 10d (IC₅₀ = 0.89 ± 0.02 µM) and 10a (IC₅₀ = 0.95 ± 0.01 µM) displayed broad spectrum anticancer activity better than the reference drug gefitinib (IC₅₀ = 0.97 ± 0.02 µM) against MCF-7. Compounds 10e (IC₅₀ = 0.28 ± 0.02 µM), 10d (IC₅₀ = 0.38 ± 0.01 µM), 7 (IC₅₀ = 0.94 ± 0.07 µM) and 10c (IC₅₀ = 1.09 ± 0.01 µM) showed better activity than the reference gefitinib (IC₅₀ = 1.30 ± 0.04 µM) against MDA-MBA-231. Moreover, EGFR and tubulin inhibition assays were performed for the highest active derivatives and showed remarkable results comparing to the reference drugs. In order to assess and explain their binding affinities, molecular docking simulation was studied against EGFR and tubulin binding sites. The results obtained from molecular docking study and those obtained from cytotoxic screening were correlated.