Randa Naffa

Synthesis, and antitumor activity of some N1-(coumarin-7-yl) amidrazones and related congeners.

A series of new N1-(coumarin-7-yl)amidrazones incorporating N-piperazines and related congeners were synthesized by reacting the hydrazonoyl chloride derived from 7-amino-4-methylcoumarin with the appropriate piperazines. The chemical structures of the newly prepared compounds were supported by elemental analyses, 1H-NMR, 13C-NMR, and ESI-HRMS spectral data. The antitumor activity of the newly synthesized compounds was evaluated. Among all the compounds tested, 7-{2-[1-(4-(1-benzyl-2-ethyl-4-nitro-1H-imidazol-5-yl)piperazin-1-yl)-2-oxopropylidene]hydrazinyl}-4-methyl-2H-chromen-2-one (3n) was the most potent against MCF-7 and K562 cells, with IC50 values of 20.2 and 9.3 μM, respectively.

Comparison of the antiproliferative activity of crude ethanol extracts of nine salvia species grown in Jordan against breast cancer cell line models.

Background: The antiproliferative activity of Salvia species grown in Jordan has not been fully evaluated yet. The aim of this work was to study the antiproliferative activity of crude ethanol extracts from nine Salvia species grown in Jordan against a panel of breast cancer cell lines. Material and Methods: Cytotoxic activity was evaluated in human tumor models of breast cancer; MCF-7, T47D, ZR-75-1, and BT 474 by the sulforhodamine B assay. In addition, the extracts were evaluated using a non-transformed cell line (Vero) and normal fibroblast cells in order to demonstrate their selectivity and safety. Results: From the nice ethanol extracts under investigation, those of S. dominica and S. fruticosa showed an inhibitory concentration of 50% of cells (IC50) in concentrations less than 30μg/mL against the four cell lines under investigation. S. syriaca and S. hormium showed an IC50 below 30μg/ml for two out of the four cell lines. S. fruticosa, S. hormium and S. syriaca showed selectivity in their antiproliferative activity against estrogen receptor positive cell lines with minimal toxicity against normal human periodontal fibroblasts. Phytochemical screening using thin layer chromatography indicated the presence of terpenoids, flavonoids and coumarins in all examined extracts. Conclusion: Three of the plant extracts under investigation exhibited antiproliferative activity against breast cancer cells and were shown to be safe and selective. These could be considered as a potential source for novel anticancer therapy.

Incidence of bcr‑abl fusion transcripts in healthy individuals.

Bcr‑abl fusion transcripts, resulting from translocation t(9;22), are hallmarks of Philadelphia chromosome positive (Ph+) leukemias. This translocation is detected in >90% of patients with chronic myelogenous leukemia and ~20% of acute lymphoblastic leukemia patients, which predominantly express the p210 and p190 proteins, respectively. Although the occurrence of t(9;22) in healthy individuals has been previously demonstrated, the number of studies is limited and the results are inconsistent. The present study screened for the presence of bcr‑abl transcripts in the blood of a group of healthy individuals using a sensitive‑nested reverse transcription polymerase chain reaction (RT‑PCR) assay. Samples were collected from 189 healthy volunteers (145 adults and 44 children). RNA was reverse transcribed and amplified by two rounds of PCR, amplifying the two common variants of bcr‑abl transcripts, p190 and p210. While the bcr‑abl p190 transcript was not detected, the p210 transcript was detected in ~10% of samples. Notably, the incidence of p210 translocation was higher in males (12.2%) compared with females (7.7%) and males were 2.4 times more likely to have the translocation. A significant incidence was also observed in adults compared with children, where adults were 6 times more likely to have the translocation. The presence of bcr‑abl transcripts in the blood of a significant proportion of healthy individuals should be considered in long‑term investigations to establish its exact association with the risk of developing leukemia. Furthermore, the current assays should be revised to consider the proportion of normal samples carrying the p210 transcripts when making a differential diagnosis.

Persistent bacteraemia due to methicillin-resistant Staphylococcus aureus with reduced susceptibility to vancomycin in a patient with erythrodermic psoriasis

A 49-y-old male with erythrodermic psoriasis developed persistent bacteraemia for 3 months due to methicillin-resistant Staphylococcus aureus despite antimicrobial therapy. The skin was the likely focus. Three consecutive isolates from the blood and 1 from the nose were identical and had vancomycin MIC of 4 mg/l.

Synthesis and biological activity assays of some new N1-(flavon-7-yl)amidrazone derivatives and related congeners.

A series of new N1-(flavon-7-yl)amidrazones incorporating N-piperazines and related congeners were synthesized by reacting the hydrazonoyl chloride derived from 7-aminoflavone and 7-amino-2-methylchromen-4-one with the appropriate piperazine. The chemical structures of the newly prepared compounds were confirmed by elemental analyses, (1)H NMR, (13)C NMR, and ESI-HRMS spectral data. The antitumor activity of these compounds was evaluated on breast cancer (MCF-7 and T47D) and Leukemic (K562) cell lines by a cell viability assay utilizing the tetrazolium dye 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT). Although with varying degrees, a significant growth inhibitory and cytotoxic effect was observed on all three cancer cell lines. Among the compounds tested compounds, 5a, 15a, and 18b, were the most active against T47D cell line with IC(50) values of 1.42, 1.92, and 2.92 μM, respectively. By using other cancer cell lines and with further characterization of their biological mechanism of action, these compounds could prove to be useful candidates as anticancer drugs.

Frequency of genetic polymorphisms of ADAM33 and their association with allergic rhinitis among Jordanians

Allergic rhinitis is a chronic inflammatory disease that is assumed to be due to an interaction between different genetic and/or environmental factors. A disintegrin and metalloprotease domain 33 (ADAM33) has been extensively studied as a susceptibility gene in asthma and has been linked to bronchial hyper-responsiveness. In this study, we investigated the association between ADAM33 single nucleotide polymorphisms and the incidence of allergic rhinitis among the Jordanian population. We conducted a case-control association study on 120 adult individuals diagnosed with allergic rhinitis and 128 normal healthy controls. 8 single-nucleotide polymorphisms in ADAM33 were genotyped using PCR-RFLP method. No significant differences in the allelic frequencies of all SNPs tested between AR patients and the control volunteers were found, although S2 C/G SNP showed a tendency toward significance with P=0.06. On the genotype level significant association were found in the following genotypes: T1 AA, T1 AG, T2 GG, T2 AG, T+1 GG, T+1 AG, V4 CG, S2 CC, S2 CG, Q-1AA. Seven haplotypes were present only within AR patients and eight haplotypes were completely absent from the AR patients. Three haplotypes exhibited significant association with AR P ≤ 0.05, two of them were present only in AR patients. In conclusion, the polymorphisms in the ADAM33 gene are associated with susceptibility to AR in the Jordanian population. Furthermore, the haplotype of the tested SNPs were also associated with the risk of AR.

Screening the Antiangiogenic Activity of Medicinal Plants Grown and Sold in Jordan

Angiogenesis is essential for the growth, invasion, and metastasis of most solid tumors and has become a valuable pharmacological target for cancer prevention and treatment. This study was performed to assess the antiangiogenic activity of 31 medicinal plants grown and sold in Jordan. The antiangiogenic activity was assessed using the rat aortic ring assay. Out of 31 extracts, 15 extracts showed more than 50 % inhibition of the blood vessels outgrowth from the primary tissue explants (p = 0.000). Three of these 15 extracts showed a potential cytotoxic effect on normal fibroblast cells. Four extracts shared antiangiogenic and antiproliferative activity towards MCF7 breast cancer cell lines. Eight extracts demonstrated selective antiangiogenic activity. This is the first report demonstrating the potential antiangiogenic activity of Artemisia judaica, Aloysia citriodora, Salvia egyptiaca, and Calendula arvensis. Some extracts with antiangiogenic activity exhibited selectivity against the endothelial cells proliferation, demonstrating a direct inhibitory activity against the key step in tumor angiogenesis.

Synthesis and Biological Activity of Some 3-(4-(Substituted)- piperazin-1-yl)cinnolines

A new series of 6-substituted-4-methyl-3-(4-arylpiperazin-1-yl)cinnolines 8–10 were synthesized as potential antifungal agents via intramolecular cyclization of the respective 1-(2-arylhydrazono)-1-(4-arylpiperazin-1-yl)propan-2-ones 5–7, mediated by polyphosphoric acid (PPA). The amidrazones themselves were synthesized via direct interaction of the appropriate hydrazonoyl chlorides 4a–d with the corresponding N-substituted piperazine in the presence of triethylamine. The structures of the new prepared compounds were confirmed by elemental analyses, 1H-NMR, 13C-NMR, and ESI-HRMS spectral data. The antitumor, antibacterial, and antifungal activity of the newly synthesized compounds was evaluated.

Relation between Copper, Lipid Profile, and Cognition in Elderly Jordanians

The purpose of the current study was to examine the association of serum copper and lipid concentrations with changes in cognitive function in elderly Jordanian individuals. The study population consisted of two groups: 52 dementia patients and 50 control subjects. All individuals were screened using the Mini-Mental State Examination and Clock Drawing Test. Serum copper and lipid profile were also assessed. Results were statistically evaluated at p < 0.05 level of significance. The dementia group had 10.1% higher copper level than control subjects that was not statistically significant. No significant differences could be found between the two groups in lipid profile levels. There was no significant correlation between serum copper, lipid profile, and cognitive decline in elderly Jordanians. Demographic variables indicated that educational level less than 12 years and illiterate demonstrated a 3.29 fold (p = 0.026) and 6.29 fold (p = 0.002) increase in risk of developing dementia, respectively. Coffee intake demonstrated a protective effect against cognitive decline with 6.25 fold lower risk with increased coffee intake.

Association Between ADAM33 Polymorphisms and Susceptibility with Adult and Childhood Asthma Among Jordanians

Disintegrin and metalloprotease 33 (ADAM33) have been associated with childhood and adult asthma in many populations. ADAM33 mutations might predispose to altered lung function in early infancy. In this study, we investigated the association between single-nucleotide polymorphisms in ADAM33 and the incidence of adult and childhood asthma among Jordanians. One hundred seven pediatric asthmatic patients, 115 healthy pediatric patient controls, 160 adult asthmatic patients, and 110 healthy adults were enrolled in this study. ADAM33 polymorphisms were genotyped using the polymerase chain reaction/restriction fragment length polymorphism method. A strong association between the V4 genotype and incidence of childhood asthma was found. In the single-locus analyses of asthma risk, V4 C/G single nucleotide polymorphism (SNP) showed a trend toward significance with p=0.07. Interestingly, the CC homozygous mutant genotype frequency was significantly higher in asthmatic subjects (15.9%) than in control subjects (2.6%), resulting in an odds ratio of 7.05. In adult cases, S2, the F+1 and Q-1 genotype showed a significant association (p≤0.05) with the incidence of asthma. Two haplotypes also exhibited a significant association with asthma (p≤0.05). In conclusion, the findings of this study confirm the already reported association between V4 SNP and the incidence of childhood asthma as well as between S2, F+1, and Q-1 SNPs and the incidence of adult asthma in several populations.