Synthesis of New Azoles and Azolopyrimidines Incorporating Morpholine Moiety as Potent Anti-Tumor Agents

A new series of morpholinyl-chalcones 2a–d was prepared by reaction of 2-oxo-N,4-diarylbut-3-enehydrazonoyl chlorides 1a–d with morpholine. These chalcones were used as a building block for constructing pyrazoles 3a–d and 3,4-dihydropyrimidine-2(1H)-thione 6 via their reaction with phenylhydrazine and thiourea, respectively. Moreover, a new series of azolopyrimidine derivatives 11a,b, 15, 17, 19, and 21 incorporating morpholine moiety were synthesized by reaction of 1-morpholino-4-phenyl-1-(2-phenylhydrazono)but-3-en-2-one (2a) with a number of heterocyclic amines in the presence of a catalytic amount of acetic acid. The assigned structures for all the newly synthesized compounds were confirmed on the basis of elemental analyses and spectral data and the mechanisms of their formation were also discussed. All the synthesized compounds were tested for in vitro activities against two antitumor cell lines, human lung cancer (A-549) and human hepatocellular carcinoma (HepG-2) compared with the employed standard antitumor drug (cisplatin) and the results revealed that compounds 6, 8c and 17 have promising activities compared with cisplatin. This work is licensed under a Creative Commons Attribution 4.0 International License

Effect of dietary honey on intestinal microflora and toxicity of mycotoxins in mice

BACKGROUND: Bee honey is a functional food which has a unique composition, antimicrobial properties and bifidogenic effect. In order to assess whether honey can inhibit the toxic effect of mycotoxins, the present study was undertaken. METHODS: Production of biomass and toxins by Aspergillus parasiticus and Aspergillus ochraceus were followed in media without and with honey. Although aflatoxins and ochratoxin A. were administrated to male Swiss albino mice up to 1 μg and 10 ng/kg body weight/day respectively. The experimental animals were fed diets without our with 10% honey for two months. The changes in colonic probiotic bacteria, determintal colon enzyme glucuronidases, and genotoxicity were followed. RESULTS: Addition of 32% in its media increased the biomass of A parasiticus, while the biomass of A. ochraceus decreased and Ochratoxin A. was not produced. When the honey was added at the ratio of 32 and 48% in the medium. No relationship was found between mycelium weight and production of mycotoxins. Oral administration of aflatoxins (mixture of B(1), B(2), G(1) and G(2)) and Ochratoxin A. induced structural and numerical chromosomal aberrations in bone marrow and germ cells of male mice, whereas, honey treatment reduced the genotoxicity of mycotoxins. Also both toxins induced histopathological changes in liver and kidney. Feeding on diet supplemented with honey improved the histopathological changes in case of aflatoxin group, but not in the case of ochratoxin A. group (except of kidney in two cases). No significant differences were found in the activity of colon β-glucuronidase between group fed diet with or without honey. On the other hand, the colon bifido bacteria and lactobacilli counts were increased markedly in group receiving diet supplemented with honey. CONCLUSION: Substituting sugars with honey in processed food can inhibit the harmful and genotoxic effects of mycotoxins, and improve the gut microflora

Rheumatological manifestations in patients with malignancies: Relation to immune modulation therapy

Background: The relation between malignancies and rheumatic diseases (RDs) is complex with commonly shared symptoms. Rheumatological manifestations of malignancies may present as paraneoplastic syndromes and could follow chemotherapy. Aim of the work: to investigate rheumatic manifestations of patients with hematologic or solid malignancies and the relation to immune-modulation therapy. Patients and methods: The study included 25 patients with hematological and another 25 with solid malignancies. Patients were subjected to medical history, recording medications received, musculoskeletal examination and laboratory assessment. Results: The mean age and F:M of patients with hematological (43.7 ± 16.04 y and F:M 1.5:1) was significantly lower than those with solid (53.6 ± 14.3 y and F:M 7.3:1) malignancies (p = 0.025 and p = 0.024). Rheumatological manifestations as the first presentation was significantly higher in patients with haematological (60%) compared to solid (20%) malignancies (p = 0.004). Articular involvement was the commonest rheumatological manifestation (72%) followed by mucocutaneous (18%), oral/genital ulcers (10%), thromboembolic events (10%), Raynauds (8%), dry eyes (8%), myositis (6%) and myalgia (4%). The total leucocytic count and serum uric acid were significantly lower in patients with solid tumors (p = 0.045 and p = 0.026 respectively) and autoimmune markers were similar. Dry eye (16.7%), oral/genital ulcers (20.8%) and Raynaud‘s (16.7%) was present only in patients receiving anti-cancer treatment (n = 24). Paradoxically, arthritis was more frequent in those not receiving chemotherapy (n = 17) while myalgia (25%) was evident in those receiving checkpoint inhibitors (n = 8). Conclusion: Rheumatological manifestations occur with solid and hematological malignancies before or throughout the disease course and the most frequent was articular. Myalgia was associated with checkpoint inhibitors

Anthropometry, laboratory, and PNPLA3 polymorphisms in a novel model for early identification and evaluation of nonalcoholic fatty liver disease

Background: Some anthropometric, laboratory, and genetic variations, such as patatin-like phospholipase domain-containing protein 3 (PNPLA3) genetic variants, have been associated with nonalcoholic fatty liver disease (NAFLD). Liver biopsy is the most accurate NAFLD diagnostic method, but it is invasive; hence, noninvasive diagnostics are required for the early diagnosis and assessment of NAFLD. Patient and methods: This prospective case-control study included 107 NAFLD patients and 107 healthy controls. All individuals underwent anthropometric measurements, abdominal ultrasonography, laboratory tests, and evaluation for PNPLA3 polymorphisms. Results: Patients with NAFLD had higher levels of C-reactive protein (CRP), tumor necrosis factor-alpha (TNF-α), and interleukin-6 (IL-6) than healthy individuals (p = 0.03, p < 0.0001). Additionally, patients with NAFLD had substantially lower albumin (P = 0.01) and leptin (P < 0.0001) levels than healthy individuals. BMI leptin and CRP levels were independent indicators of NAFLD severity (p = 0.05–0.004). GG is the most prevalent genotype in patients with moderate to severe NAFLD. A novel model based on four markers (leptin, CRP, BMI, and PNPLA3 polymorphism) was developed. The AUC values for distinguishing between the healthy subjects and those with varying degrees of NAFLD severity (mild, moderate, and severe) were 0.99, 0.99, and 1.0, respectively. Conclusion: Anthropometric measurements, such as BMI and laboratory results, including liver enzymes, CRP, inflammatory markers, lipid parameters, and genetic markers, especially PNPLA3 polymorphisms, can provide an accurate, sensitive, and specific noninvasive approach for the early identification and assessment of NAFLD and can guide its management. This may minimize the need for liver biopsy to assess NAFLD. Further large-scale studies are needed to confirm these findings and verify the model in larger studies