Browsing by Author "Shadrack, Daniel M."

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    In Silico Evaluation of Anti-Malarial Agents from Hoslundia opposita as Inhibitors of Plasmodium falciparum Lactate Dehydrogenase (P f LDH) Enzyme
    (Scientific Research, 2016-06-17) Shadrack, Daniel M.; Nyandoro, Stephen S.; Munissi, Joan J. E.; Mubofu, Egid B.
    Malaria has continued to be a health and economic problem in Africa and the world at large. Many anti-malarial drugs have been rendered ineffective due to the emergence of resistant strains of Plamodium falciparum. A key malaria parasite enzyme in glycolytic pathway, P. falciparum lactate dehydrogenase (PfLDH) is specially targeted for anti-malarial drugs development. Thus, the aim of this investigation was to determine the in silico inhibition effects of antimalarial compounds from Hoslundia opposita Vahl. namely hoslundin, hoslundal and hoslunddiol on PfLDH enzyme. The compounds were docked to the three-dimensional structure of PfLDH as enzyme using AutoDock Vina in PyRx virtual screening software. Binding affinity and position of the inhibitors were evaluated using PyMol software. The PfLDH enzyme showed two binding sites: the cofactors binding site (Site A) and secondary binding site (Site B). In the absence of the cofactor all ligands showed higher affinity than NADH, and were bound to the cofactors binding site (Site A). When docked in the presence of the cofactor, site B was the preferred binding site. Binding to cofactor site with higher binding energy than NADH suggests that these ligands could act as preferential competitive inhibitors of PfLDH. However, the binding to site B also suggests that they may be non-competitive allosteric inhibitors. Amino acid residues Gly99, Asn140, Phe100 and Thr97 were indicated to form hydrogen bonds with Hoslundin. Hoslunddiol showed hydrogen bonding with Thr97 and Met30, while Hoslundal formed hydrogen bond with Thr101 and Asn140.
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    Synthesis of Polyamidoamine Dendrimer for Encapsulating Tetramethylscutellarein for Potential Bioactivity Enhancement
    (2015-11) Shadrack, Daniel M.; Mubofu, Egid B.; Nyandoro, Stephen S.
    The biomedical potential of flavonoids is normally restricted by their low water solubility. However, little has been reported on their encapsulation into polyamidoamine (PAMAM) dendrimers to improve their biomedical applications. Generation four (G4) PAMAM dendrimer containing ethylenediaminetetraacetic acid core with acrylic acid and ethylenediamine as repeating units was synthesized by divergent approach and used to encapsulate a flavonoid tetramethylscutellarein (TMScu, 1) to study its solubility and in vitro release for potential bioactivity enhancement. The as-synthesized dendrimer and the dendrimer–TMScu complex were characterized by spectroscopic and spectrometric techniques. The encapsulation of 1 into dendrimer was achieved by a co-precipitation method with the encapsulation efficiency of 77.8% ˘ 0.69% and a loading capacity of 6.2% ˘ 0.06%. A phase solubility diagram indicated an increased water solubility of 1 as a function of dendrimer concentration at pH 4.0 and 7.2. In vitro release of 1 from its dendrimer complex indicated high percentage release at pH 4.0. The stability study of the TMScu-dendrimer at 0, 27 and 40 ˝ C showed the formulations to be stable when stored in cool and dark conditions compared to those stored in light and warmer temperatures. Overall, PAMAM dendrimer-G4 is capable of encapsulating 1, increasing its solubility and thus could enhance its bioactivity.
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    Synthesis of Polyamidoamine Dendrimer for Encapsulating Tetramethylscutellarein for Potential Bioactivity Enhancement
    (2015) Shadrack, Daniel M.; Mubofu, Egid B.; Nyandoro, Stephen S.
    The biomedical potential of flavonoids is normally restricted by their low water solubility. However, little has been reported on their encapsulation into polyamidoamine (PAMAM) dendrimers to improve their biomedical applications. Generation four (G4) PAMAM dendrimer containing ethylenediaminetetraacetic acid core with acrylic acid and ethylenediamine as repeating units was synthesized by divergent approach and used to encapsulate a flavonoid tetramethylscutellarein (TMScu, 1) to study its solubility and in vitro release for potential bioactivity enhancement. The as-synthesized dendrimer and the dendrimer–TMScu complex were characterized by spectroscopic and spectrometric techniques. The encapsulation of 1 into dendrimer was achieved by a co-precipitation method with the encapsulation efficiency of 77.8% ± 0.69% and a loading capacity of 6.2% ± 0.06%. A phase solubility diagram indicated an increased water solubility of 1 as a function of dendrimer concentration at pH 4.0 and 7.2. In vitro release of 1 from its dendrimer complex indicated high percentage release at pH 4.0. The stability study of the TMScu-dendrimer at 0, 27 and 40 °C showed the formulations to be stable when stored in cool and dark conditions compared to those stored in light and warmer temperatures. Overall, PAMAM dendrimer-G4 is capable of encapsulating 1, increasing its solubility and thus could enhance its bioactivity.