67 research outputs found

    Adamantyl-tethered-biphenylic compounds induce apoptosis in cancer cells by targeting Bcl homologs

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    Bcl homologs prominently contribute to apoptotic resistance in cancer cells and serve as molecular targets in treatment of various cancers. Herein, we report the synthesis of biphenyl-adamantane derivatives by a ligand free palladium on carbon based Suzuki reaction using diisopropylamine as a base for the coupling of adamantane based aryl chloride with a variety of aryl boronic acids. Among the biphenyl derivatives synthesized, compound 3'-(adamantan-1-yl)-4'-methoxy-1,1'-biphenyl-3-ol (AMB) displayed cytotoxic activity against hepatocellular carcinoma cell lines without significantly affecting the normal cell lines. Further, AMB caused increased accumulation of the HCC cells in subG1 phase, decreased the expression of Bcl-2, Bcl-xL, cyclin D1, caspase-3, survivin and increased the cleavage of PARP in a time-dependent manner. In silico molecular interaction studies between Bcl homologs and AMB showed that the biphenyl scaffold is predicted to form �-� interactions with Phe-101 and Tyr-105 and the adamantyl fragment is predicted to occupy another hydrophobic region in the kink region of the binding groove. In summary, we report on the synthesis and biological characterization of adamantyl-tethered biphenylic compounds that induce apoptosis in tumor cells most likely by targeting Bcl homologs. © 2015 Elsevier Ltd

    Postoperative complications after procedure for prolapsed hemorrhoids (PPH) and stapled transanal rectal resection (STARR) procedures

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    Procedure for prolapsing hemorrhoids (PPH) and stapled transanal rectal resection for obstructed defecation (STARR) carry low postoperative pain, but may be followed by unusual and severe postoperative complications. This review deals with the pathogenesis, prevention and treatment of adverse events that may occasionally be life threatening. PPH and STARR carry the expected morbidity following anorectal surgery, such as bleeding, strictures and fecal incontinence. Complications that are particular to these stapled procedures are rectovaginal fistula, chronic proctalgia, total rectal obliteration, rectal wall hematoma and perforation with pelvic sepsis often requiring a diverting stoma. A higher complication rate and worse results are expected after PPH for fourth-degree piles. Enterocele and anismus are contraindications to PPH and STARR and both operations should be used with caution in patients with weak sphincters. In conclusion, complications after PPH and STARR are not infrequent and may be difficult to manage. However, if performed in selected cases by skilled specialists aware of the risks and associated diseases, some complications may be prevented

    Role of epigenetics in inflammation-associated diseases.

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    Sub-cellular biochemistry61627-65

    The role of pro-inflammatory molecules and pharmacological agents in acute pancreatitis and sepsis

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    Inflammation and Allergy - Drug Targets9120-3

    Aminooxyacetate inhibits hydrogen sulfide and ammonium synthesis and protects mice in acute pancreatitis

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    International Journal of Integrative Biology817-1

    Molecular targets of celastrol derived from Thunder of God Vine: Potential role in the treatment of inflammatory disorders and cancer

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    10.1016/j.canlet.2010.10.025Cancer Letters30319-20CALE

    Targeting cell signaling and apoptotic pathways by dietary agents: Role in the prevention and treatment of cancer

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    10.1080/01635581.2011.523502Nutrition and Cancer632161-173NUCA

    Role of NF-κB in tumorigenesis

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    10.1615/ForumImmunDisTher.2013008382Forum on Immunopathological Diseases and Therapeutics42181-19
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