Cancer is considered one of the top global causes of death. Natural products have been used in oncology medicine either in crude form or by utilizing isolated secondary metabolites. Biologically active phytomolecules such as gallic acid and quercetin have confirmed antioxidant, anti-bacterial, and neoplastic properties. There is an agreement that microorganisms could mediate oncogenesis or alter the immune system. This research project aims to develop a novel formulation of co-loaded gallic acid and quercetin into nanoliposomes and investigate the efficacy of the free and combined agents against multiple cancerous cell lines and bacterial strains. Thin-film hydration technique was adopted to synthesize the nanocarriers. Particle characteristics were measured using a Zetasizer. The morphology of nanoliposomes was examined by scanning electron microscopy, Encapsulation efficiency and drug loading were evaluated using High-Performance Liquid Chromatography. Cytotoxicity was determined against Breast Cancer Cells MCF-7, Human Carcinoma Cells HT-29, and A549 Lung Cancer Cells. The antibacterial activities were evaluated against Acinetobacter baumannii, Escherichia coli, Proteus mirabilis, Pseudomonas aeruginosa, and Staphylococcus aureus. Therapeutic formulas were categorized into groups: free gallic acid, free quercetin, free-mix, and their nano-counterparts. Findings revealed that drug loading capacity was 0.204 for the mix formula compared to 0.092 and 0.68 for free gallic acid and quercetin, respectively. Regarding the Zeta potential, the mix formula showed more amphiphilic charge than the free quercetin and free gallic acid formulas (P-values 0.003 and 0.002 receptively). On the contrary, no significant difference in polydispersity indices was reported. Lung cancerous cells were the most affected by the treatments. The best estimated IC50 values were observed in breast and lung cancer lines for the nano-gallic acid and co-loaded particles. The nano-quercetin formula exhibited the least cytotoxicity with an IC50 value of ≥200 μg/mL in both breast (MCF-7) and colorectal adenocarcinoma cell lines (HT-29) with no activity against the lung. A remarkable improvement in the efficacy of quercetin was measured after mixing it with gallic acid against the breast and lungs. The tested therapeutic agents exhibited antimicrobial activity against gram-positive bacteria. Nano-liposomes can either enhance or reduce the cytotoxicity activity of active compounds depending on the physical and chemical properties of drug-loaded and type of cancer cells.

Summary: Erwinia amylovora causes fire blight on several plant species such as apple and pear, which produce diverse phytoalexins as defence mechanisms. An evolutionary successful pathogen thus must develop resistance mechanisms towards these toxic compounds. The E. amylovora outer membrane protein, TolC, might mediate phytoalexin resistance through its interaction with the multidrug efflux pump, AcrAB. To prove this, a tolC mutant and an acrB/tolC double mutant were constructed. The minimal inhibitory concentrations of diverse antimicrobials and phytoalexins were determined for these mutants and compared with that of a previously generated acrB mutant. The tolC and arcB/tolC mutants were considerably more susceptible than the wild type but showed similar levels as the acrB mutant. The results clearly indicated that neither TolC nor AcrAB significantly interacted with other transport systems during the efflux of the tested toxic compounds. Survival and virulence assays on inoculated apple plants showed that pathogenicity and the ability of E. amylovora to colonize plant tissue were equally impaired by mutations of tolC and acrB/tolC . Our results allowed the conclusion that TolC plays an important role as a virulence and fitness factor of E. amylovora by mediating resistance towards phytoalexins through its exclusive interaction with AcrAB.

Helicobacter pylori infection can lead to gastritis, peptic ulcer, and the development of mucosa associated lymphoid tissue (MALT) lymphoma. Treatment and eradication of H. pylori infection can prevent relapse and accelerate the healing of gastric and duodenal ulcers as well as regression of malignancy. Due to the increasing emergence of antibiotic resistance among clinical isolates of H. pylori, alternative approaches using newly discovered antimicrobial agents in combination with the standard antibiotic regimens for the treatment of H. pylori are of major importance. The purpose of the present study was to investigate the effect of newly synthesized 8-amino 7-substituted fluoroquinolone and their correspondent cyclized triazolo derivatives when either alone or combined with metronidazole against metronidazole-resistant H. pylori. Based on standard antimicrobial susceptibility testing methods and checkerboard titration assay, all of the tested compounds showed interesting antimicrobial activity against 12 clinical strains of H. pylori, with best in vitro effect for compounds 4b and 4c. Fractional inhibitory concentration (FIC) mean values showed synergistic pattern in all compounds of Group 5. In addition, additive activities of some of the tested compounds of Group 4 were observed when combined with metronidazole. In contrast, the tested compounds showed no significant urease inhibition activity. These results support the potential of new fluoroquinolone derivatives to be useful in combination with anti-H. pylori drugs in the management of H. pylori-associated diseases.