• Phytochemical Investigation and Anticancer Evaluation of Pimenta dioica (Allspice) Berries

      Capito, Jason E.; Lokeshwar, Bal L.; Panda, Siva S.; Department of Chemistry & Physics (2017-03)
      Cancer of the prostate (CaP) is the most common non-skin cancer in American men. As the disease recurs over several years in a significant fraction of patients, it is a good target for chemoprevention. If began early, preventive agents may enhance the survival and quality of the patients’ life profoundly such that the disease, even if not completely eliminated, may pose little threat to life. Recurrent CaP following radiation therapy, surgery or both is incurable at present. All studies reported to date state that conventional chemotherapy is used with limited effect, prolonging life between 2 and 4 months. Many aromatic tropical plants contain a rich assortment of secondary metabolites that are evolved to protect and preserve the nutrients from bacterial, fungal and insect infestations. These include alkaloids, glycosides, polyphenols, terpenes and terpenoids. Several compounds with pharmacological activities have been isolated from fresh leaves of Pimenta dioica (Family: Myrtaceae; alternate name: Jamaican pepper) and the dried, unripe berries, known as allspice, are marketed as an edible spice. Allspice, which tastes like a blend of cloves, nutmeg, cinnamon and pepper, is a common flavoring compound in Asian, Middle Eastern and Jamaican cuisines. In this study, the bioassay, isolation and phytochemical investigation of active component from the aromatic berries of Pimenta dioica (allspice) were carried out. Potential antitumor activities of allspice extract and a compound purified from the extract were tested against prostate and breast cancer cell lines.
    • Purification of Recombinant Human Histone Methyltransferases for Inhibition Studies

      Jahan, Asmat; Shaikh, Zahid; Department of Chemistry & Physics (2017-03)
      Resistance to cellular apoptotic pathways is a major contributing factor in the metastasis of cancer. One such cell-intrinsic pathway which induces programmed cell death is ligand cell surface death receptors, including Fas protein. In primary colorectal cancer, Fas expression is often diminished. The silencing of Fas expression is perhaps a mechanism by which human colorectal cancer cells evade apoptosis. The decrease in Fas expression levels is associated with hypermethylation of histone 3 lysine 9 catalyzed by histone methyltransferases (HMTases) such as SUV39H1 and SUV39H2. Because of the role of methylation in silencing Fas expression, HMTase inhibitors represent potential anti-cancer agents. Verticillin A, a natural compound extracted from wild mushroom, is a broad-based HMTase inhibitor and has been shown to cause toxicity in mice. Our goal in this study is to identify specific SUV39H1 and SUV39H2 inhibitors that are less toxic than Verticillin A. To investigate this, human SUV39H1 was sub-cloned into an expression vector, transformed into an E.coli expression strain and purified using affinity chromatography. Gel electrophoresis and Western blot analysis confirmed the presence of partially purified human SUV39H1. The next phase of the project will involve testing the activity of the purified protein in an in vitro assay.
    • Synthesis, Antibacterial Properties and Molecular Modeling Studies of Quinolone-triazole Hybrids

      Honkanadavar, Hitesh; Panda, Siva S.; Department of Chemistry & Physics (2017-03)
      Quinolones are one of the most important synthetic antibacterial agents and have been widely used in the treatment of diverse infections including urinary tract, respiratory and bone joint infections as well as sexually transmitted diseases, prostatitis, pneumonia and acute bronchitis. However, quinolone resistance increases in almost all Gram-negative and Gram-positive species as well as tuberculosis. The continued increase in resistance has put enormous pressure on public health systems worldwide, mainly due to the high level of use and to some degree of abuse. The current study deals with bio-conjugation of quinolone antibiotics, including ciprofloxacin, norfloxacin, and pipemidic acid (considering that the pyridopyrimidinyl nucleus is the bio-isosteric form of the quinoline ring), with triazole rings. Interest in the 1,2,3-triazol scaffold for developing novel bio-conjugates is attributed to the pharmacological properties exhibited by 1,2,3-triazole containing-compounds as anti-inflammatory, anti-tumor, and antibacterial agents. Additionally, 1,2,3-triazole possesses favorable properties in the medicinal chemistry field. It has a moderate dipole character, hydrogen bonding capability, rigidity and remarkable metabolic stability. In a previous study, it was found that antibiotic conjugates with amino acids enhance the lipophilic properties of quinolone antibiotics with a retention or increase in antibacterial activity. In the current study, a 1,2,3-triazole nucleus is being introduced into amino acid and antibiotic conjugates to alter their biological properties. Computational chemistry studies including 3D-pharmacophore and 2D-QSAR (quantitative structure-activity relationship) are being used to assist in the understanding of observed biological properties as well as determining the most important structural parameters controlling bio-activity. These studies are also being used to validate observed biological data.