RESUMO
The synthesis and biological activity of a variety of analogues to the naturally occurring antibacterial and antifungal Distamycin A were explored by a number of authors. These compounds were subject to a large array of assays. Some of these compounds showed high activity against a range of Gram-positive, Gram-negative bacteria as well as fungi. To explore the anti-parasitic activity of this class of compounds, specific modifications had to be made. A number of these compounds proved to be active against Trypanosoma brucei. The binding of a number of these compounds to short sequences of DNA were also examined using footprinting assays as well as NMR spectroscopy. Computer modelling was employed on selected compounds to understand the way these compounds bind to specific DNA sequences. A large number of variations were made to the standard structure of Distamycin. These changes involved the replacement of the pyrrole moieties as well as the head and tail groups with a number of heterocyclic compounds. Some of these minor groove binders (MGBs) were also investigated for their capability for the treatment of cancer and in particular lung cancer.
Assuntos
DNA/metabolismo , Distamicinas/metabolismo , Animais , Antibacterianos/química , Antibacterianos/metabolismo , Antibacterianos/farmacologia , Simulação por Computador , DNA/química , Pegada de DNA , Distamicinas/química , Distamicinas/farmacologia , Humanos , Espectroscopia de Ressonância Magnética , Tripanossomicidas/química , Tripanossomicidas/metabolismo , Tripanossomicidas/farmacologiaRESUMO
This article describes a multidisciplinary approach to a functional and aesthetic rehabilitation. In this case study, we successfully corrected an anterior open bite and an exaggerated curve of Spee using restorative modalities while still maintaining a highly aesthetic outcome. The maxillary anterior teeth no longer appear to have a disproportional width/length ratio and are now in harmony with the mandibular veneers. Posterior function was re-established, mostly with implant-retained crowns. Occlusal harmony and stability are maintained through cuspid guidance and anterior disclusion. Proper selection of final restorative materials is imperative for the long-term survival of the restorations.