Expansion of the Structure-Activity Relationship Profile of Triaminopyrimidines as Inhibitors of Caspase-1.

Caspase-1 is a sought-after therapeutic target for inflammatory conditions due to its role in activation and release of pro-inflammatory cytokines, but there has been little success getting drugs into the clinic. We have previously shown triaminopyrimidines such as CK-1-41 are potent, reversible small molecule inhibitors of caspase-1, likely binding in an allosteric site within the enzyme. A series of analogs of CK-1-41 were synthesized and tested against caspase-1 to develop a more robust structure-activity relationship profile.

3-(4-Iodo-phen-yl)-2,3-di-hydro-1-benzo[]chromen-1-one.

In the title compound, CHIO, the dihedral angle between the naphthyl ring system and the pendant iodo-phenyl ring is 72.48 (11)°. In the crystal, C-H⋯π inter-actions and I⋯O [3.

Biomaterials Enabled Cell-Free Strategies for Endogenous Bone Regeneration.

Repairing bone defects poses a major orthopedic challenge because current treatments are constrained by the limited regenerative capacity of human bone tissue. Novel therapeutic strategies, such as stem cell therapy and tissue engineering, have the potential to enhance bone healing and regeneration, and hence may improve quality of life for millions of people. However, the ex vivo expansion of stem cells and their in vivo delivery pose technical difficulties that hamper clinical translation and commercial development.

Visualization of mercury(ii) accumulation in vivo using bioluminescence imaging with a highly selective probe.

Mercury is a highly toxic environmental pollutant that negatively affects human health. Thus, an in vivo method for noninvasive imaging of mercury(ii) and visualization of its accumulation within living systems would be advantageous. Herein, we describe a reaction-based bioluminescent probe for detection of mercury(ii) in vitro and accumulation in vivo.

Design, Synthesis, and Evaluation of (2-(Pyridinyl)methylene)-1-tetralone Chalcones for Anticancer and Antimicrobial Activity.

Background: Chalcones, natural products produced by plants as a natural defense mechanisms against various pathogens, are molecules with structures that include two aromatic rings joined by an α, β unsaturated carbonyl system. Previous research has demonstrated that chalcones exhibit a wide variety of biological activities, including anticancer, antifungal, and antibiotic properties.

Objective: Our goal is to synthesize novel heterocyclic-containing chalcones and have their biological activities evaluated.

Design and synthesis of benzopyran-based inhibitors of the hypoxia-inducible factor-1 pathway with improved water solubility.

While progress has been made in treating cancer, cytotoxic chemotherapeutic agents are still the most widely used drugs and are associated with severe side-effects. Drugs that target unique molecular signalling pathways are needed for treating cancer with low or no intrinsic toxicity to normal cells. Our goal is to target hypoxic tumours and specifically the hypoxia inducible factor (HIF) pathway for the development of new cancer therapies.

Examining the structure-activity relationship of benzopyran-based inhibitors of the hypoxia inducible factor-1 pathway.

Many forms of solid tumor have a characteristic feature known as hypoxia, which describes a low or non-existent presence of oxygen in the cellular microenvironment. This decrease in oxygen causes activation of the hypoxia inducible factor (HIF) pathway, which activates the transcription of many genes that cause cell proliferation, metastasis, increased glycolysis and angiogenesis. Increased HIF expression has been linked with poor patient prognosis, increased malignancy, and therapeutic resistance.

Crystal structure of (E)-2-[(2-bromopyridin-3-yl)methyl-idene]-6-meth-oxy-3,4-di-hydro-naphthalen-1(2H)-one and 3-[(E)-(6-meth-oxy-1-oxo-1,2,3,4-tetra-hydro-naphthalen-2-ylidene)meth-yl]pyridin-2(1H)-one.

The title compounds C17H14BrNO2, (I), and C17H15NO3, (II), were obtained from the reaction of 6-meth-oxy-3,4-di-hydro-2H-naphthalen-1-one and 2-bromo-nicotinaldehyde in ethanol. Compound (I) was the expected product and compound (II) was the oxidation product from air exposure. In the crystal structure of compound (I), there are no short contacts or hydrogen bonds.

Crystal structure of (E)-1-(3-chloro-phen-yl)-3-(furan-2-yl)prop-2-en-1-one.

The title compound, C13H9ClO2, exhibits a non-planar geometry; the furan ring being inclined to the benzene ring by 50.52 (16)°. In the crystal, mol-ecules stack along the a axis; however, there are no significant inter-molecular inter-actions present.

Core-Scaffold-Inspired Asymmetric Synthesis of Polysubstituted Chiral Hexahydropyridazines that Potently Inhibit Breast Cancer Cell Proliferation by Inducing Apoptosis.

The highly enantioselective preparation of pharmacologically interesting hexahydropyridazine derivatives based on a multicomponent cascade reaction is described. This one-pot approach utilizes an organocatalytic Michael reaction followed by intermolecular α-amination and intramolecular hemiaminalization to yield a chiral pyridazine backbone with contiguous stereogenic centers and multiple functional groups in good yield and with high stereoselectivity. Compounds synthesized by this method potently inhibited proliferation of MCF-7 breast cancer cells.

Synthesis and in vitro evaluation of 4-substituted furano[3,2-c] tetrahydroquinolines as potential anti-cancer agents.

A convenient and mild method for the synthesis of substituted furano [3,2-c]tetrahydroquinoline derivatives was developed, using the multi-component Povarov reaction. Of the synthesized tetrahydroquinoline derivatives, compound 10a displayed the greatest cellular proliferation inhibitory activities with IC50 values of 2.5-16.