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Saccharomonospora sp. UR22 and Dietzia sp. UR66, two actinomycetes derived from the Red Sea sponge Callyspongia siphonella, were co-cultured and the induced metabolites were monitored by HPLC-DAD and TLC. Saccharomonosporine A (1), a novel brominated oxo-indole alkaloid, convolutamydine F (2) along with other three known induced metabolites (3-5) were isolated from the EtOAc extract of Saccharomonospora sp. UR22 and Dietzia sp. UR66 co-culture. Additionally, axenic culture of Saccharomonospora sp. UR22 led to isolation of six known microbial metabolites (6-11). A kinase inhibition assay results showed that compounds 1 and 3 were potent Pim-1 kinase inhibitors with an IC50 value of 0.3 ± 0.02 and 0.95 ± 0.01 μM, respectively. Docking studies revealed the binding mode of compounds 1 and 3 in the ATP pocket of Pim-1 kinase. Testing of compounds 1 and 3 displayed significant antiproliferative activity against the human colon adenocarcinoma HT-29, (IC50 3.6 and 3.7 μM, respectively) and the human promyelocytic leukemia HL-60, (IC50 2.8 and 4.2 μM, respectively). These results suggested that compounds 1 and 3 act as potential Pim-1 kinase inhibitors that mediate the tumor cell growth inhibitory effect. This study highlighted the co-cultivation approach as an effective strategy to increase the chemical diversity of the secondary metabolites hidden in the genomes of the marine actinomycetes.

Fungi usually contain gene clusters that are silent or cryptic under normal laboratory culture conditions. These cryptic genes could be expressed for a wide variety of bioactive compounds. One of the recent approaches to induce production of such cryptic fungal metabolites is to use histone deacetylases (HDACs) inhibitors. In the present study, the cultures of the marine-derived fungus Penicillium brevicompactum treated with nicotinamide and sodium butyrate were found to produce a lot of phenolic compounds. Nicotinamide treatment resulted in the isolation and identification of nine compounds 1–9. Sodium butyrate also enhanced the productivity of anthranilic acid (10) and ergosterol peroxide (11). The antioxidant as well as the antiproliferative activities of each metabolite were determined. Syringic acid (4), sinapic acid (5), and acetosyringone (6) exhibited potent in vitro free radical scavenging, (IC50 20 to 30 µg/mL) and antiproliferative activities (IC50 1.14 to 1.71 µM) against HepG2 cancer cell line. Furthermore, a pharmacophore model of the active compounds was generated to build up a structure-activity relationship.

Phytochemical investigation of Flacourtia rukam Zoll. & Mortizi (F. rukam) leaves and bark led to the isolation and characterization of seventeen compounds of which four phenolics were not previously described; 2-[(benzoyloxy)methyl]-phenyl-O-β-xylosyl-(1→2)-βglucopyranoside (1), 2-[(benzoyloxy)methyl]-4-hydroxyphenyl-O-β-xylosyl-(1→2)-β-Dglucopyranoside (2), 2-hydroxy-5-(2-hydroxyphenoxy)phenoxy-β-glucopyranoside (3) andbiphenyl-1,1′,2,2′-tetraol (5). Interestingly, the later compound is known as a synthetic but this is the first report for its isolation from nature. Chemical structures were established using extensive analysis of spectroscopic data (1D and 2D NMR and HRESIMS). Biphenyl-1,1,2,2′tetrol (5) exhibited a good activity against Trypanosoma brucei trypamastigotes with IC50= 6.66 ug/mL. Compounds 2, 5, 9, 10, 11 and 12 showed a good in-vitro anti-inflammatory activity using proteinase inhibitory assay. On the contrary, all tested compounds were inactive as antileishmanial or antimalarial.

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Background: Huge volumes of local anaesthetics used in conventional blocks may be associated with complications. Hyaluronidase is an enzyme that hydrolyses hyaluronic acid in the tissue. It has been shown to aid the spread of local anaesthetics (LA) through tissue. The aim of this study was to compare between the addition of morphine or hyaluronidase to local anaesthetic in sonar guided supraclavicular brachial plexus block regarding the onset and duration of the block, postoperative analgesia and the total analgesic requirements in the first 24 hours. Patient and methods: Seventy-five patients of American Society of Anaesthesiologists (ASA) physical status I & II, aged 18-60 years, scheduled to acute or elective elbow, forearm or hand surgery under sonar guided supraclavicular brachial plexus block at Tanta University Hospital were randomly allocated into three equal groups; Group I (Control group) received 20 ml containing 9 ml bupivacaine 0.5% and 9 ml lidocaine 2% plus 2 ml normal saline, group II (Morphine group) received 20 ml containing 9 ml bupivacaine 0.5% and 9 ml lidocaine 2% plus 5 mg morphine in 2 ml normal saline and group III (Hyaluronidase group) received 20 ml containing 9 ml bupivacaine 0.5% and 9 ml lidocaine 2% plus 1500 units of hyaluronidase in 2 ml normal saline. The onset of sensory and motor block, duration of sensory and motor block, postoperative VAS, time to first rescue analgesia, total morphine consumption and possible side effects were recorded. Results: Onset of the sensory block and motor block was significantly shorter in the hyaluronidase group than control group and morphine group. Duration of the sensory block and motor block was significantly prolonged in morphine group than hyaluronidase group & control group. VAS started to increase at 6 hours in the control group, at 10 hours in morphine group and at 8 hours in hyaluronidase group. Time to first rescue analgesia was significantly prolonged in morphine group than control group and hyaluronidase group. Total analgesic consumption of morphine was significantly lower in morphine group than control group and hyaluronidase group. Conclusion: Morphine was superior to hyaluronidase as regarding to improving the post-operative pain. The incidence of complications was nil and self-limited in the three groups.