Analysis of Floral Sources of a Local Honey Used in Clinical Treatment of Topical Community Acquired Methicillin Resistant .

A study was initiated during the summers of 2015-2019 to characterize the floral and chemical components in a local honey (clinical honey) that was being used in a Food and Drug Administration (FDA) approved clinical study designed to evaluate effectiveness in controlling topical community acquired methicillin resistant (caMRSA) infections. Floral sources were determined by collecting nectar and pollen from plants visited by bees within the area where the local honey is being produced (Study Area). Pollen characteristics were determined by using both light microscopy (LM) and scanning electron microscopy (SEM).

Cystargolide-based amide and ester Pz analogues as proteasome inhibitors and anti-cancer agents.

A series of cystargolide-based β-lactone analogues containing nitrogen atoms at the Pz portion of the scaffold were prepared and evaluated as proteasome inhibitors, and for their cytotoxicity profile toward several cancer cell lines. Inclusion of one, two or even three nitrogen atoms at the Pz portion of the cystargolide scaffold is well tolerated, producing analogues with low nanomolar proteasome inhibition activity, in many cases superior to carfilzomib. Additionally, analogue , containing an ester and pyrazine group at Pz, was shown to possess significant activity toward RPMI 8226 cells (IC = 21 nM) and to be less cytotoxic toward the normal tissue model MCF10A cells than carfilzomib.

A toxicological study on photo-degradation products of environmental ibuprofen: Ecological and human health implications.

Increasing quantities of pharmaceutical waste in the environment have disrupted the balance of ecosystems, and may have subsequent effects on human health. Although a handful of previous studies have shown the impacts of pharmaceutically active compounds on the environment, the toxicological effects of their degradation products remain largely unknown. In the current study, the photo-degradation products of environmental ibuprofen were assessed for both ecotoxicological and human health effects using a series of in vitro assays.

Design, synthesis, and evaluation of cystargolide-based β-lactones as potent proteasome inhibitors.

The peptidic β-lactone proteasome inhibitors (PIs) cystargolides A and B were used to conduct structure-activity relationship (SAR) studies in order to assess their anticancer potential. A total of 24 different analogs were designed, synthesized and evaluated for proteasome inhibition, for cytotoxicity towards several cancer cell lines, and for their ability to enter intact cells. X-ray crystallographic analysis and subunit selectivity was used to determine the specific subunit binding associated with the structural modification of the β-lactone (P), peptidic core, (P and P), and end-cap (P) of our scaffold.

A total synthesis of (-)-Hortonone C.

A total synthesis of the cytotoxic terpenoid hortonone C was accomplished and its absolute stereochemistry confirmed. Intermediate (+)- was synthesized using either an asymmetric conjugate addition strategy, or by elaboration of the Hajos-Parrish ketone. Reduction of (+)- under dissolving-metal conditions and trapping the enolate intermediate served to control the cis-stereochemistry at the ring fusion and provide a silyl enol ether necessary for ring expansion.

Total synthesis and absolute stereochemistry of the proteasome inhibitors cystargolides A and B.

The absolute stereochemistry of the cystargolides was determined by total synthesis. Evaluation of synthetic cystargolides and derivatives showed that the natural (2S,3R) stereochemistry is essential for activity. Moreover, benzyl esters (-)-10 and (-)-15 were found to be about 100 times more potent, and to selectively kill MCF-7 cancerous cells.

Detailed analysis of (-)-palmyrolide a and some synthetic derivatives as voltage-gated sodium channel antagonists.

A small library of synthetic (-)-palmyrolide A diastereomers, analogues, and acyclic precursors have been examined with respect to their interaction with voltage-gated sodium channels (VGSCs). Toward this goal, the ability of (-)-palmyrolide A and analogues to antagonize veratridine-stimulated Na(+) influx in primary cultures of mouse cerebrocortical neurons was assessed. We found that synthetic (-)-palmyrolide A and its enantiomer functioned as VGSC antagonists to block veratridine-induced sodium influx.

Ligand and substrate effects during Pd-catalyzed cyclizations of alkyne-tethered cyclohexadienones.

The effects of ligand and substrate choice on the Pd-catalyzed cyclization of alkyne-tethered cyclohexadienones were examined. In the presence of a chiral ligand, the enantioselectivity of the desymmetrization is remarkably sensitive to structural changes in both the ligand and the substrate. Additionally, the regioselectivity of the reaction (5- vs.

Bicyclic Cyclohexenones as Inhibitors of NF-κB Signaling.

A series of structurally simplified cryptocaryone analogues were synthesized by a facile Pd-catalyzed acetoxylation of alkyne-tethered cyclohexadienones and evaluated as inhibitors of NF-κB signaling. Compounds 10 and 11 were found to possess low micromolar inhibitory properties towards induced NF-κB activity by blocking p50/p65 nuclear protein through a covalent inhibition mechanism. Both compounds were able to inhibit NF-κB-induced IL-8 expression and exhibited antiproliferative activity against two model cancer cell lines.

Evolution of a protecting-group-free total synthesis: studies en route to the neuroactive marine macrolide (-)-palmyrolide A.

A full account of our synthetic work toward the first total synthesis of the neuroactive marine macrolide (-)-palmyrolide A is described. Our first-generation approach aimed to unlock the unknown C(5)-C(7) stereochemical relationship via the synthesis of four diastereomers of palmyrolide A aldehyde, a known degradation product. When these efforts provided inconclusive results, recourse to synthesizing all possible stereocombinations of the 15-membered macrolide was undertaken.

Asymmetric total synthesis and absolute stereochemistry of the neuroactive marine macrolide palmyrolide A.

The first asymmetric total synthesis and determination of the absolute configuration for the neuroactive marine macrolide palmyrolide A is described. The highlight of the synthesis is macrocyclization via trans-enamide formation catalyzed by copper(I) iodide and cesium carbonate. Comparison with the authentic spectral data confirms the synthesis of (+)-ent-palmyrolide A.

Regioselective and stereoselective cyclizations of cyclohexadienones tethered to active methylene groups.

The cyclization of 2,5-cyclohexadienones tethered to activated methylene groups was studied. The substitution around the cyclohexadienone ring serves to regioselectively direct these cyclizations based primarily on electronic effects. In the case of brominated substrates, these reactions proceed to give highly unusual electron-deficient tricyclic cyclopropanes.

Palladium-catalyzed reactions of cyclohexadienones: regioselective cyclizations triggered by alkyne acetoxylation.

Regioselective cyclizations of alkyne-tethered cyclohexadienones can be accomplished under palladium catalysis. The cyclization involves an initial Pd-mediated acetoxylation of the alkyne, followed by migratory insertion and protonolysis of the resulting palladium enolate. The predictable regioselectivity of these atom-economical and stereoselective reactions is influenced by developing steric interactions during migratory insertion of a vinyl palladium intermediate.

A formal synthesis of the auriside aglycon.

A highly convergent formal synthesis of the auriside aglycon was achieved. An indene-based thiazolidinethione chiral auxiliary was used for the construction of both the C1-C9 and C10-C17 fragments via acetate aldol reactions. A Meinwald reaction was utilized to install the stereocenter at C2, and a conjugated addition to an ynone was used to construct the C9-C11 enone.