Aromatase (CYP19) catalyzes the aromatization reaction of androgen substrates to estrogens, the last and rate-limiting step in estrogen biosynthesis. Inhibition of aromatase is a new and promising approach to treat hormone-dependent breast cancer. We present here the design and development of isoflavanone derivatives as potential aromatase inhibitors. Structural modifications were performed on the A and B rings of isoflavanones via microwave-assisted, gold-catalyzed annulation reactions of hydroxyaldehydes and alkynes. The in vitro aromatase inhibition of these compounds was determined by fluorescence-based assays utilizing recombinant human aromatase (baculovirus/insect cell-expressed). The compounds 3-(4-phenoxyphenyl)chroman-4-one (1h), 6-methoxy-3-phenylchroman-4-one (2a) and 3-(pyridin-3-yl)chroman-4-one (3b) exhibited potent inhibitory effects against aromatase with IC50 values of 2.4 μM, 0.26 μM and 5.8 μM, respectively. Docking simulations were employed to investigate crucial enzyme/inhibitor interactions such as hydrophobic interactions, hydrogen bonding and heme iron coordination. This report provides useful information on aromatase inhibition and serves as a starting point for the development of new flavonoid aromatase inhibitors.

In this study, we evaluated the abilities of a series of chalcones to inhibit the activity of the enzyme xanthine oxidase (XO) and to scavenge radicals. 20 mono- and polyhydroxylated chalcone derivatives were synthesized by Claisen-Schmidt condensation reactions and then tested for inhibitory potency against XO, a known generator of reactive oxygen species (ROS). In parallel, the ability of the synthesized chalcones to scavenge a stable radical was determined. Structure-activity relationship analysis in conjunction with molecular docking indicated that the most active XO inhibitors carried a minimum of three hydroxyl groups. Moreover, the most effective radical scavengers had two neighboring hydroxyl groups on at least one of the two phenyl rings. Since it has been proposed previously that XO inhibition and radical scavenging could be useful properties for reduction of ROS-levels in tissue, we determined the chalcones’ effects to rescue neurons subjected to ROS-induced stress created by the addition of β-amyloid peptide. Best protection was provided by chalcones that combined good inhibitory potency with high radical scavenging ability in a single molecule, an observation that points to a potential therapeutic value of this compound class.

CdTe quantum dots (QDs) were synthesized by a modified hydrothermal method with Na 2 TeO 3 as the Te source. Thioglycolic acid (TGA), thiolactic acid (TLA), 3mercaptopropionic acid (MPA), 3-mercaptobutyric acid (3MBA), 4-mercaptobutyric acid (MBA), and 5-mercaptovaleric acid (MVA) were used. Their effects on the growth and fluorescence of as-synthesized QDs were investigated: Detrimental precursor aggregation when using TGA-like molecules (TGA and L-cysteine) due to their special secondary coordination was observed and further confirmed by comparing with DL-homocysteine and N-acetyl-L-cysteine. The aggregation could be suppressed by using a bulky methyl group as a side chain to confine the carboxyl group, that is, TLA. Moreover, MPA was confirmed as a better stabilizer compared with linear TGA, MBA, and MVA probably because of its suitable balance between hydrophilicity and hydrophobicity. Accordingly, we designed and synthesized 3MBA that has the same main chain length as MPA but with a side methyl group as TLA. 3MBA-modified CdTe QDs exhibited an excellent optical property with a quantum yield of 71%, much higher than that of MPA and TGA. Preliminary results of CdSe QDs confirmed the versatility of 3MBA. Our results uncovered the possible origin of the advantages of mercapto acids with a methyl side chain and a suitable chain length.

Four new benzofuran-type stilbene glycosides and 14 known compounds including 8 benzofuran-type stilbenes and 6 flavonoids were isolated from the traditional Chinese medicine, Cortex Mori Radicis. The new compounds were identified as (9R)-moracin P 3′-O-α-l-arabinopyranoside (1), (9R)-moracin P 9-O-β-d-glucopyranoside (2), (9R)-moracin P 3′-O-β-d-glucopyranoside (3), and (9R)-moracin O 10-O-β-d-glucopyranoside (4) based on the spectroscopic interpretation and chemical analysis. Three benzofuran-type stilbenes, moracin O (5), R (7), and P (8) showed significant neuroprotective activity against glutamate-induced cell death in SK-N-SH cells. In addition, moracin O (5) and P (8) also demonstrated a remarkable inhibition of the acetic acid-induced pain. The molecular docking with metabotropic glutamate receptor 1 (mGluR1) results indicated that these neuroprotective benzofuran-type stilbenes might be the active analgesic components of the genus Morus, and acted by mediating the mGluR1 pathway.

Lithium, sodium, and potassium enolates reacted with bisaminoboron halides to give bisaminoboron enolates 1a-5c. Specifically, the potassium enolate of tert-butyl methyl ketone reacted with bis-(diisopropylamino)boron chloride in THF at room temperature within 1 h to give the bis(diisopropylamino)-boron enolate of tert-butyl methyl ketone (3b) in 61-84% isolated yields. Under similar conditions, the reactivity is highly dependent on the metal employed to generate enolates (K > Na > Li) as well as the nitrogen substituents in the bisaminoboron halides (iPr > Et > TMS). This latter observation is a compromise between the boron-nitrogen resonance and the steric effect. The structural information of enolate 3b was studied in detail. Unlike the aggregated alkali-metal enolates, this boron enolate exists exclusively as a monomer in both the solid and solution states, as identified by X-ray and diffusionordered NMR.

Fluorinated isoflavanones and bifunctionalized isoflavanones were synthesized through a one-step gold(I)-catalyzed annulation reaction. These compounds were evaluated for their in vitro inhibitory activities against aromatase in a fluorescence-based enzymatic assay. Selected compounds were tested for their anti-proliferative effects on human breast cancer cell line MCF-7. Compounds 6-methoxy-3-(pyridin-3-yl)chroman-4-one (3c) and 6-fluoro-3-(pyridin-3-yl)chroman-4-one (3e) were identified as the most potent aromatase inhibitors with IC50 values of 2.5 μM and 0.8 μM. Therefore, these compounds have great potential for the development of pharmaceutical agents against breast cancer.

Edema Factor toxin (EF) of Bacillus anthracis (NIAID category A), and several other toxins from NIAID category B Biodefense target bacteria are adenylyl cyclases or adenylyl cyclase agonists that catalyze the conversion of ATP to 3′,5′-cyclic adenosine monophosphate (cAMP). We previously identified compound 1 (3-[(9-Oxo-9H-fluorene-1-carbonyl)-amino]-benzoic acid), that inhibits EF activity in cultured mammalian cells, and reduces diarrhea caused by enterotoxigenic Escherichia coli (ETEC) at an oral dosage of 15 μg/mouse. Here, molecular docking was used to predict improvements in potency and solubility of new derivatives of compound 1 in inhibiting edema toxin-(ET) catalyzed stimulation of cyclic AMP production in murine monocyte-macrophage cells (RAW 264.7). Structure-activity relationship (SAR) analysis of the bioassay results for 22 compounds indicated positions important for activity. Several derivatives demonstrated superior pharmacological properties compared to our initial lead compound, and are promising candidates to treat anthrax infections and diarrheal diseases induced by toxin-producing bacteria.

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