Classification and treatment of Class II subdivision malocclusions.

Introduction: Patients with Class II subdivision malocclusions are a challenge for clinicians because reestablishing symmetry in 1 arch or both arches is often a treatment goal. In patients with mandibular skeletal asymmetry, surgery is often a treatment option. However, patients may be unwilling to undergo surgery, and other options might have to be considered.

Tethered thiazolidinone dimers as inhibitors of the bacterial type III secretion system.

Disruption of protein-protein interactions by small molecules is achievable but presents significant hurdles for effective compound design. In earlier work we identified a series of thiazolidinone inhibitors of the bacterial type III secretion system (T3SS) and demonstrated that this scaffold had the potential to be expanded into molecules with broad-spectrum anti-Gram negative activity. We now report on one series of thiazolidinone analogs in which the heterocycle is presented as a dimer at the termini of a series of linkers.

Design and synthesis of bis-carbamate analogs of cyclic bis-(3'-5')-diguanylic acid (c-di-GMP) and the acyclic dimer PGPG.

The bacterial second messenger cyclic bis-(3'-5')-diguanylic acid (c-di-GMP) regulates diverse Gram-negative bacterial virulence functions. The pathways that control, or are controlled by, c-di-GMP suggest that c-di-GMP signaling systems may encompass potential drug targets. It is presently undetermined, however, whether up- or down-modulation of c-di-GMP signaling would be the desired therapeutic state.

Substituted 2-imino-5-arylidenethiazolidin-4-one inhibitors of bacterial type III secretion.

Diverse species of pathogenic Gram-negative bacteria use secretion systems to export a variety of protein toxins and virulence factors that help establish and maintain infection. Disruption of such secretion systems is a potentially effective therapeutic strategy. We developed a high-throughput screen and identified a tris-aryl substituted 2-imino-5-arylidenethiazolidin-4-one, compound 1, as an inhibitor of the type III secretion system.

An inhibitor of gram-negative bacterial virulence protein secretion.

Bacterial virulence mechanisms are attractive targets for antibiotic development because they are required for the pathogenesis of numerous global infectious disease agents. The bacterial secretion systems used to assemble the surface structures that promote adherence and deliver protein virulence effectors to host cells could comprise one such therapeutic target. In this study, we developed and performed a high-throughput screen of small molecule libraries and identified one compound, a 2-imino-5-arylidene thiazolidinone that blocked secretion and virulence functions of a wide array of animal and plant Gram-negative bacterial pathogens.

Rearrangement of a Tricyclic 2,5-Cyclohexadienone: Towards a General Synthetic Route to the Daphnanes and (+)-Resiniferatoxin.

Light as a reagent: A highly functionalized structure that serves as a daphnane template can be formed by the photorearrangement of a 2,5-cyclohexadienone subunit within a complex tricyclic ring system. The chemistry we describe should not only find use in the total synthesis of resiniferatoxin and related daphnanes, but should also provide useful templates for access to complex analogues.