Rula M. Darwish

Screening of antibiotic resistant inhibitors from local plant materials against two different strains of Staphylococcus aureus

The inhibitory effects of methanolic extracts of 19 Jordanian plants and their combinations with seven antibiotics, on the resistance of Staphylococcus aureus were checked. Methicillin resistant S. aureus (MRSA), which was isolated from patient and a standard strain of S. aureus were used. Our results showed that there are variations in the effect of some combinations used on the resistant and the standard strains probably due to structural changes. Common results between the two strains showed that combinations of gentamicin and chloramphenicol could be improved by the use of plant materials, whereas nalidixic acid activity cannot be improved when combined with plant materials.

Effect of ethnomedicinal plants used in folklore medicine in Jordan as antibiotic resistant inhibitors on Escherichia coli

BackgroundEscherichia coli occurs naturally in the human gut; however, certain strains that can cause infections, are becoming resistant to antibiotics. Multidrug-resistant E. coli that produce extended-spectrum β lactamases (ESBLs), such as the CTX-M enzymes, have emerged within the community setting as an important cause of urinary tract infections (UTIs) and bloodstream infections may be associated with these community-onsets. This is the first report testing the antibiotic resistance-modifying activity of nineteen Jordanian plants against multidrug-resistant E. coli.MethodsThe susceptibility of bacterial isolates to antibiotics was tested by determining their minimum inhibitory concentrations (MICs) using a broth microdilution method. Nineteen Jordanian plant extracts (Capparis spinosa L., Artemisia herba-alba Asso, Echinops polyceras Boiss., Gundelia tournefortii L, Varthemia iphionoides Boiss. & Blanche, Eruca sativa Mill., Euphorbia macroclada L., Hypericum trequetrifolium Turra, Achillea santolina L., Mentha longifolia Host, Origanum syriacum L., Phlomis brachydo(Boiss.) Zohary, Teucrium polium L., Anagyris foetida L., Trigonella foenum-graecum L., Thea sinensis L., Hibiscus sabdariffa L., Lepidium sativum L., Pimpinella anisum L.) were combined with antibiotics, from different classes, and the inhibitory effect of the combinations was estimated.ResultsMethanolic extracts of the plant materials enhanced the inhibitory effects of chloramphenicol, neomycin, doxycycline, cephalexin and nalidixic acid against both the standard strain and to a lesser extent the resistant strain of E. coli. Two edible plant extracts (Gundelia tournefortii L. and Pimpinella anisum L.) generally enhanced activity against resistant strain. Some of the plant extracts like Origanum syriacum L.(Labiateae), Trigonella foenum- graecum L.(Leguminosae), Euphorbia macroclada (Euphorbiaceae) and Hibiscus sabdariffa (Malvaceae) did not enhance the activity of amoxicillin against both standard and resistant E. coli. On the other hand combinations of amoxicillin with other plant extracts used showed variable effect between standard and resistant strains. Plant extracts like Anagyris foetida (Leguminosae) and Lepidium sativum (Umbelliferae) reduced the activity of amoxicillin against the standard strain but enhanced the activity against resistant strains. Three edible plants; Gundelia tournefortii L. (Compositae) Eruca sativa Mill. (Cruciferae), and Origanum syriacum L. (Labiateae), enhanced activity of clarithromycin against the resistant E. coli strain.ConclusionThis study probably suggests possibility of concurrent use of these antibiotics and plant extracts in treating infections caused by E. coli or at least the concomitant administration may not impair the antimicrobial activity of these antibiotics.

Screening of antibiotic resistant inhibitors from local plant materials against two different strains of Pseudomonas aeruginosa

The methanolic extracts of 19 Jordanian plants were combined with seven different antibiotics and applied to check the inhibitory effects of the combination on the resistance of Pseudomonas aeruginosa. A resistant strain of Ps. aeruginosa, which was isolated from a patient and a standard strain of the same microorganism were used in this study. Our results showed that there are significant variations in the effects of some combinations used on the resistant and the standard strains probably due to structural changes. Almost all the plant materials used in combination with penicillin G and erythromycin allowed full growth of the standard strain, while the combination with some plant materials like Gundelia tournefortii L. and Lepidium sativum L. inhibited the growth of the resistant strain. Chloramphenicol, gentamicin and cephalosporin can be given advantageously with almost all the plant materials used with few exceptions on the resistant strain. Nalidixic acid activity was improved significantly when combined with all plant materials and tested on standard strain. On the other hand, its activity on the resistant strain was slightly improved using the same combinations.

Synthesis and Antibacterial Properties of New 8-Nitrofluoroquinolone Derivatives

The objective of this research was the preparation of new 8-nitrofluoroquinolone models and investigation of their antibacterial properties. The work initially involved large scale preparation of the synthon 7-chloro-1-cyclopropyl-6-fluoro-8-nitro-4-oxo-1,4-dihydroquinoline-3-carboxylic acid (3), followed by introduction of substituted primary amine appendages at the C-7 position to give derivatives 9a-g, in which the amino group is appended to substituted benzenes or aromatic heterocycles, is part of a primary alpha-amino acid or just a simple primary aliphatic amine. This nucleophilic aromatic substitution step was a very simple procedure since the 8-nitro group of the above synthon facilitated the addition of weak nucleophiles at C-7. All compounds prepared were fully identified and characterized using NMR, IR, EA and MS, and were consistent with expected structures. The prepared targets and the intermediates have shown interesting antibacterial activity against gram positive and/or gram negative strains. In particular, the p-toluidine, p-chloroaniline and aniline derivatives showed good activity against S. aureus with MIC range approximately 2-5 microg/mL. In conclusion, more lipophilic groups seem to enhance activity against gram positive strains.

Effect of chemosensitizers on minimum inhibitory concentrations of fluconazole in Candida albicans.

Objective: To evaluate the effect of chemosensitizers on the in vitro activity of fluconazole against Candida albicans strains. Materials and Methods: Using Clinical Laboratory Standard Institute method, antifungal activity of fluconazole was determined alone and in combination with 16 chemosensitizers that included verapamil, reserpine, quinine, quinidine, gemfibrozil, lansoprazole, tamoxifen, diltiazem, desipramine, nicardipine, cyclosporine, chlorpromazine, prochlorperazine, promethazine, thioridazine, and trifluoperazine. Further studies were done using double combinations of selected chemosensitizers with fluconazole (28 combinations). For testing combinations, half of the minimum inhibitory concentration (MIC) of each agent was selected in order to avoid the effect of the drug alone. One reference strain (ATCC90028) and one clinical isolate of C. albicans were used for testing the in vitro activity. Broth dilution method was used to determine the MICs of fluconazole and chemosensitizers. Results: Of the 16 chemosensitizers tested, 3 exhibited in vitro activity by increasing fluconazole susceptibility to 7-fold. The MICs of the reference strain and clinical isolate for fluconazole were 5.5 and 0.55 µg/ml, respectively, and these were reduced to 0.76 µg/ml by gemfibrozil, 0.83 µg/ml by quinine, and 0.76 µg/ml by chlorpromazine in the reference strain, with MIC reduction to 0.08 µg/ml by all three chemosensitizers in the clinical isolate. Some double combinations reduced the MIC of fluconazole to 10- to 100-fold, even when the chemosensitizers were not effective alone. Conclusion: The most effective double combinations were those of chlorpromazine with either reserpine or nicardipine.

New form of administering chlorhexidine for treatment of denture-induced stomatitis

Background: The purpose of this study was to evaluate the release of chlorhexidine as an antifungal drug from doped self-cured poly (methyl methacrylate) (PMMA) acrylic resin and the effect of the drug released on the growth of Candida albicans. Methods: Release of chlorhexidine was evaluated using liquid chromatography, and the effect of the drug on the growth of C. albicans was investigated microbiologically using a “well” technique on Saboraud culture medium inoculated with a resistant strain of C. albicans. Results: Chlorhexidine leached steadily out of the acrylic resin into distilled water at mouth temperature, and the sustained drug release continued throughout the 28-day test period. The drug released also demonstrated antifungal activity against the resistant strain of C. albicans. Conclusion: The findings of this study support the use of chlorhexidine-impregnated self-cured PMMA chair-side resin as a new dosage form for the treatment of denture-induced stomatitis.

Diversity and distribution of entomopathogenic nematodes (Nematoda: Steinernematidae, Heterorhabditidae) and their bacterial symbionts (γ-Proteobacteria: Enterobacteriaceae) in Jordan

Until now, only a few systematic surveys of entomopathogenic nematodes (EPN) have been conducted in Middle Eastern countries. Many of the recovered EPN species in this region have shown to own distinctive qualities that enable their survival in unique environments, such as high temperatures and low moisture levels tolerance. These new species and strains, with unique environmental tolerances, are more suitable for their consideration in pest management programs in xerophytic regions. With this background in mind, we recently conducted a survey of EPN in Jordan. This study records for the first time the diversity and distribution of these nematodes and their bacterial symbionts in this country. Jordans three geographic regions: (1) the highlands, (2) Jordan valley and (3) the desert region were sampled. Within each region, natural habitats and agricultural regions characteristic to each region were considered for sampling purposes. Four EPN species including three Steinernema and one Heterorhabditis were recovered. Nematodes were identified using a combination of molecular markers and classic morphological diagnostic tools. Bacterial symbionts were identified by analysis of 16S rRNA sequences. Abiotic characteristics such as soil type, soil pH, and elevation were also recorded. We herein report the diversity of EPN species in Jordan and discuss their potential in Biocontrol and IPM programs for this country.

Chemical constituents of Jordanian propolis

Seventeen compounds, including a new lanostane triterpenoid, 24(Z)-1β-3β-dihydroxyeupha-7,24-dien-26-oic acid, have been isolated from the methanolic extracts of two samples of Jordanian propolis collected from two different places with different dominant flora. The structures of the isolated compounds were elucidated by spectral methods including IR, UV, MS and 1- and 2-D NMR.

Synthesis of New Nitrofluoroquinolone Derivatives with Novel Anti-Microbial Properties against Metronidazole Resistant H. pylori

One of the major therapeutic approaches to preventing relapse and accelerating the healing of duodenal and gastric ulcers is the eradication of Helicobacter pylori. Due to the emergence of antibiotic resistance among clinical strains of H. pylori, alternative approaches using newly discovered antimicrobial agents in combination with the standard regimens for the treatment of H. pylori are increasingly needed. The purpose of the present study was to investigate the effect of newly synthesized 8-nitroflouroqunolone derivatives when used either alone or when combined with metronidazole against metronidazole-resistant H. pylori. Based on the 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 the best in vitro effect for compound 3c. In addition, synergistic and additive activities of some of the tested compounds were observed when combined with metronidazole. Furthermore, among the tested nitroflouroquinolone derivatives, compound 3b showed significant urease inhibition activity with IC50 of 62.5 µg/mL. These results suggest that 8-nitroflouroquinolone derivatives may have a useful role in combination with anti-H. pylori drugs in the management of H. pylori-associated diseases.

Synthesis of 1,2,3-Triazolo[4,5-h]quinolone Derivatives with Novel Anti-Microbial Properties against Metronidazole Resistant Helicobacter pylori

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.