Synthesis, Characterization, Antibacterial and Anti-Inflammatory Activities of Enoxacin Metal Complexes

The present work comprises the synthesis of enoxacin (Heno) complexes with various transition metals. Two types of complexes [M(eno)2(H2O)2]3H2O(M = CuII, NiII or MnII) and [M(eno)(H2O)2]Cl · 4H2O (M = FeIII) were obtained. The complexes were characterized by different physicochemical, spectroscopic, and elemental analysis. Results suggest that enoxacin interacts with the metals as a monoanionic bidentate ligand. These complexes were also tested for their antibacterial activity against eleven (11) different microorganisms, and the results were compared with the parent drug. Moreover all the metal complexes were also tested for their ability to scavenge reactive oxygen species where by MnII and CuII complexes exhibited potential to mediate anti-inflammatory response

IMMUNOMODULATORY ACTIVITIES OF SOME COMMON LICHEN METABOLITES

Objective: To evaluate the immunomodulatory activities of some of the common lichen compounds by using chemiluminescence based cellular assays.Methods: Number of secondary lichen metabolites, representing a breadth of lichen substances, were investigated for their effects on the respiratory burst of human whole blood phagocytes, isolated human polymorphonuclear leukocytes (PMNs) and murine macrophages using luminol or lucigenin-based chemiluminescence probes. Results: This study identify a clear suppressive effect of some lichen metabolites on phagocytosis response upon activation with serum opsonized zymosan by several lichen substances. Amongst the compounds tested, orsellinic acid, methyl orsellinate, methyl haematomate, lecanoric acid and lobaric acid, showed a potent immunomodulatory activity as compared to the standards. The lobaric acid suppressed both the myloperoxidase dependent and myloperoxidase independent, Reactive Oxygen Species (ROS) production in the oxidative burst of polymorphonuclear neutrophils (PMN) at the lowest concentration tested (3.1 µg/ml). Whereas, lecanoric acid, suppressed only the myloperoxidase dependent ROS production with IC50< 3.1µg/ml when compared to the standard sodium diethyldithiocarbamate trihydrate (SDT) (IC50 = 1.3 ± 0.2 µg/ml). Orsellinic acid, methyl orsellinate and methyl haematomate showed a selective myloperoxidase independent pathway with IC50 values; < 3.1µg/ml; 6.1 ± 1.0 µg/ml;  3.3 ± 0.1 µg/ml, respectively, being lower as compared to standard SDT (IC50 = 8.2 ± 1.9 µg/ml). Conclusion: Based on the results obtained it is appropriate to conclude that lichen are not only a good source of antioxidants, but also potent immunomodulators, and thus deserve to be investigated further.Â

Cheiradone: a vascular endothelial cell growth factor receptor antagonist

<p>Abstract</p> <p>Background</p> <p>Angiogenesis, the growth of new blood vessels from the pre-existing vasculature is associated with physiological (for example wound healing) and pathological conditions (tumour development). Vascular endothelial growth factor (VEGF), fibroblast growth factor-2 (FGF-2) and epidermal growth factor (EGF) are the major angiogenic regulators. We have identified a natural product (cheiradone) isolated from a <it>Euphorbia </it>species which inhibited <it>in vivo </it>and <it>in vitro </it>VEGF- stimulated angiogenesis but had no effect on FGF-2 or EGF activity. Two primary cultures, bovine aortic and human dermal endothelial cells were used in <it>in vitro </it>(proliferation, wound healing, invasion in Matrigel and tube formation) and <it>in vivo </it>(the chick chorioallantoic membrane) models of angiogenesis in the presence of growth factors and cheiradone. In all cases, the concentration of cheiradone which caused 50% inhibition (IC₅₀) was determined. The effect of cheiradone on the binding of growth factors to their receptors was also investigated.</p> <p>Results</p> <p>Cheiradone inhibited all stages of VEGF-induced angiogenesis with IC₅₀values in the range 5.20–7.50 μM but did not inhibit FGF-2 or EGF-induced angiogenesis. It also inhibited VEGF binding to VEGF receptor-1 and 2 with IC₅₀values of 2.9 and 0.61 μM respectively.</p> <p>Conclusion</p> <p>Cheiradone inhibited VEGF-induced angiogenesis by binding to VEGF receptors -1 and -2 and may be a useful investigative tool to study the specific contribution of VEGF to angiogenesis and may have therapeutic potential.</p

4-(2-Methoxy­benzyl­idene)-2-phenyl-1,3-oxazol-5(4H)-one

The title mol­ecule, C17H13NO3, adopts a Z configuration about the central olefinic bond. The 2-phenyl ring is almost coplanar with the plane of the oxazolone ring system, making a dihedral angle of 2.03 (11)°. The crystal structure is stabilized by π–π inter­actions between the oxazolone ring and phenyl ring of a neighbouring mol­ecule [centroid–centroid distance = 3.550 (3)Å], and by two weak inter­molecular C—H⋯π inter­actions. In addition, the crystal structure exhibits one weak intra­molecular C—H⋯N hydrogen bond

In Vivo Anti-Inflammatory, Anti-Bacterial and Anti-Diarrhoeal Activity of Ziziphus Jujuba Fruit Extract

BACKGROUND: Ziziphus jujuba belongs to family Rhamnaceae widely distributed in subtropical and tropical countries. It is used traditionally for several pharmacological purposes including anti-inflammation, antidiarrhoeal and antibacterial, as well as tonic and sometimes as hypnotic (sedative).AIM: To determine the in vivo antidiarrhoeal, antibacterial and anti-inflammatory activities of Z. jujuba fruit ethanolic extract.METHOD: The fruit was macerated and extracted by 95% (v/v) ethanol. The antidiarrhoeal activity was evaluated using castor oil and Escherichia coli induced diarrhoea mouse model. The antidiarrhoeal and antibacterial activity was investigated at graded doses (400-1200 mg/kg). The anti-inflammatory effects were tested using the carrageenan-induced paw oedema in female Wistar rats. Rat’s treatment groups received tragacanth, 100 mg/kg diclofenac sodium, 800 mg/kg, 1200 mg/kg or 1600 mg/kg of an ethanolic extract of Z. jujuba (EEZJ). All treatment groups were fed with the compounds one hour before carrageenan injection at of rat’s paw. Also, the EEZJ was further analysed by HPLC-PDA system for identification of the presence of betulinic acid and quercetin.RESULTS: EEZJ different doses did not show inhibitory activity against castor oil induced diarrhoea except for the higher (1200 mg/kg) dose. However, the frequency of defecation of stools and watery stool were reduced significantly when compared to control group (P ≤ 0.05 and P ≤ 0.01 respectively), resulted in overall 67% inhibition of diarrhoea. Our anti-inflammatory results demonstrated that EEZJ was able to inhibit the carrageenan-induced paw oedema in rats to a significant degree (p ≤ 0.05) and the paw volume and thickness of both left and right paw were affected compared to the negative control group.CONCLUSION: EEZJ possesses antidiarrhoeal and antibacterial activity in a dose depending manner and may provide a pharmacological basis for its clinical use in diarrheal diseases. The activity may partially be due to the presence of betulinic acid and quercetin

Total synthesis, structural, and biological evaluation of stylissatin A and related analogs

The natural product cyclic peptide stylissatin A (1a) was reported to inhibit nitric oxide production in LPS-stimulated murine macrophage RAW 264.7 cells. In the current study, solid-phase total synthesis of stylissatin A was performed by using a safety-catch linker and yielded the peptide with a trans-Phe7-Pro6 linkage, whereas the natural product is the cis rotamer at this position as evidenced by a marked difference in NMR chemical shifts. In order to preclude the possibility of 1b being an epimer of the natural product, we repeated the synthesis using d-allo-Ile in place of l-Ile and a different site for macrocyclization. The resulting product (d-allo-Ile2)-stylissatin A (1c) was also found to have the trans-Phe7-Pro6 peptide conformations like rotamer 1b. Applying the second route to the synthesis of stylissatin A itself, we obtained stylissatin A natural rotamer 1a accompanied by rotamer 1b as the major product. Rotamers 1a, 1b, and the epimer 1c were separable by HPLC, and 1a was found to match the natural product in structure and biological activity. Six related analogs 2–7 of stylissatin A were synthesized on Wang resin and characterized by spectral analysis. The natural product (1a), the rotamer (1b), and (d-allo-Ile2)-stylissatin A (1c) exhibited significant inhibition of NO.. Further investigations were focused on 1b, which also inhibited proliferation of T-cells and inflammatory cytokine IL-2 production. The analogs 2–7 weakly inhibited NO. production, but strongly inhibited IL-2 cytokine production compared with synthetic peptide 1b. All analogs inhibited the proliferation of T-cells, with analog 7 having the strongest effect. In the analogs, the Pro6 residue was replaced by Glu/Ala, and the SAR indicates that the nature of this residue plays a role in the biological function of these peptides. Copyright © 2016 European Peptide Society and John Wiley & Sons, Ltd

Effects of Hibiscus sabdariffa on high blood pressure, lipid profile and C- reactive protein among adult hypertensive patients

BackgroundHypertension is a leading cause of mortality and morbidity worldwide. Hibiscus is a cheap readily available preparation.AimsWe aimed to assess the effect of Hibiscus sabdariffa on blood pressure, lipid profile, plasma sugar, and h-sensitive C-reactive protein.MethodsThis is a prospective cohort study conducted among 19 College staff members at the University of Tabuk, Saudi Arabia during January 2020. The participants signed written informed consent, then responded to a questionnaire to report their demographic data. At baseline,  the blood pressure was measured, anthropometric measures collected, and, and a blood sample was taken to measure fasting plasma sugar, serum cholesterol, triglycerides, high-density lipoproteins, and high-sensitive C-reactive protein. Participants thereafter took Hibiscus sabdariffa for four weeks, then the above measurements were repeated. The compliance of the participants was also assessed.Results No significant effects of Hibiscus sabdariffa consumption were observed on systolic and diastolic blood pressure, fasting plasma glucose, lipid profile, and high-sensitive C-reactive protein, P-value< 0.05.ConclusionNo significant effects were observed among Hibiscus sabdariffa users on blood pressure, plasma sugar, lipid profile, and C-reactive protein. Further larger multicenter studies are recommended

Acetonic Extract of Buxus sempervirens Induces Cell Cycle Arrest, Apoptosis and Autophagy in Breast Cancer Cells

Plants are an invaluable source of potential new anti-cancer drugs. Here, we investigated the cytotoxic activity of the acetonic extract of Buxus sempervirens on five breast cancer cell lines, MCF7, MCF10CA1a and T47D, three aggressive triple positive breast cancer cell lines, and BT-20 and MDA-MB-435, which are triple negative breast cancer cell lines. As a control, MCF10A, a spontaneously immortalized but non-tumoral cell line has been used. The acetonic extract of Buxus sempervirens showed cytotoxic activity towards all the five studied breast cancer cell lines with an IC50 ranging from 7.74 µg/ml to 12.5 µg/ml. Most importantly, the plant extract was less toxic towards MCF10A with an IC50 of 19.24 µg/ml. Fluorescence-activated cell sorting (FACS) analysis showed that the plant extract induced cell death and cell cycle arrest in G0/G1 phase in MCF7, T47D, MCF10CA1a and BT-20 cell lines, concomitant to cyclin D1 downregulation. Application of MCF7 and MCF10CA1a respective IC50 did not show such effects on the control cell line MCF10A. Propidium iodide/Annexin V double staining revealed a pre-apoptotic cell population with extract-treated MCF10CA1a, T47D and BT-20 cells. Transmission electron microscopy analyses indicated the occurrence of autophagy in MCF7 and MCF10CA1a cell lines. Immunofluorescence and Western blot assays confirmed the processing of microtubule-associated protein LC3 in the treated cancer cells. Moreover, we have demonstrated the upregulation of Beclin-1 in these cell lines and downregulation of Survivin and p21. Also, Caspase-3 detection in treated BT-20 and T47D confirmed the occurrence of apoptosis in these cells. Our findings indicate that Buxus sempervirens extract exhibit promising anti-cancer activity by triggering both autophagic cell death and apoptosis, suggesting that this plant may contain potential anti-cancer agents for single or combinatory cancer therapy against breast cancer

Withanolides and related steroids

Since the isolation of the first withanolides in the mid-1960s, over 600 new members of this group of compounds have been described, with most from genera of the plant family Solanaceae. The basic structure of withaferin A, a C28 ergostane with a modified side chain forming a δ-lactone between carbons 22 and 26, was considered for many years the basic template for the withanolides. Nowadays, a considerable number of related structures are also considered part of the withanolide class; among them are those containing γ-lactones in the side chain that have come to be at least as common as the δ-lactones. The reduced versions (γ and δ-lactols) are also known. Further structural variations include modified skeletons (including C27 compounds), aromatic rings and additional rings, which may coexist in a single plant species. Seasonal and geographical variations have also been described in the concentration levels and types of withanolides that may occur, especially in the Jaborosa and Salpichroa genera, and biogenetic relationships among those withanolides may be inferred from the structural variations detected. Withania is the parent genus of the withanolides and a special section is devoted to the new structures isolated from species in this genus. Following this, all other new structures are grouped by structural types. Many withanolides have shown a variety of interesting biological activities ranging from antitumor, cytotoxic and potential cancer chemopreventive effects, to feeding deterrence for several insects as well as selective phytotoxicity towards monocotyledoneous and dicotyledoneous species. Trypanocidal, leishmanicidal, antibacterial, and antifungal activities have also been reported. A comprehensive description of the different activities and their significance has been included in this chapter. The final section is devoted to chemotaxonomic implications of withanolide distribution within the Solanaceae. Overall, this chapter covers the advances in the chemistry and biology of withanolides over the last 16 years.Fil: Misico, Rosana Isabel. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Departamento de Química Orgánica; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Unidad de Microanálisis y Métodos Físicos Aplicados a la Química Orgánica (i); ArgentinaFil: Nicotra, V.. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Córdoba. Instituto Multidisciplinario de Biología Vegetal (p); Argentina. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas. Departamento de Química Orgánica; ArgentinaFil: Oberti, Juan Carlos María. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Córdoba. Instituto Multidisciplinario de Biología Vegetal (p); Argentina. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas. Departamento de Química Orgánica; ArgentinaFil: Barboza, Gloria Estela. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Córdoba. Instituto Multidisciplinario de Biología Vegetal (p); Argentina. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas. Departamento de Farmacia; ArgentinaFil: Gil, Roberto Ricardo. University Of Carnegie Mellon; Estados UnidosFil: Burton, Gerardo. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Departamento de Química Orgánica; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Unidad de Microanálisis y Métodos Físicos Aplicados a la Química Orgánica (i); Argentin