Biomedical subjects

Hong Hu

Publications and source records attributed to Hong Hu.

22 records · Page 2Linked to original sources

PubMed2002

Synthesis and protein kinase inhibitory activity of balanol analogues with modified benzophenone subunits.

A series of analogues of the protein kinase C (PKC) inhibitory natural product balanol which bear modified benzophenone subunits are described. The analogues were designed with the goal of uncovering structure-activity features that could be used in the development of PKC inhibitors with a reduced polar character compared to balanol itself. The results of these studies suggest that most of the benzophenone features found in the natural product are important for obtaining potent PKC inhibitory compounds. However, several modifications were found to lead to selective inhibitors of the related enzyme protein kinase A (PKA), and several specific modifications to the polar structural elements of the benzophenone were found to provide potent PKC inhibitors. In particular, it was found that replacement of the benzophenone carboxylate with bioisosteric equivalents could lead to potent analogues. Further, a tolerance for lipophilic substituents on the terminal benzophenone ring was uncovered. These results are discussed in light of recently available structural information for PKA.

Azepines↗

PubMed2002

Exceptional survival of a patient with large ventricular septal defect, bidirectional shunt, and severe pulmonary valve stenosis.

A 74-year-old man has survived in good health for an exceptionally long time despite the presence of a moderate-to-large-sized membranous ventricular septal defect (VSD). He has remained acyanotic with New York Heart Association class I function. Transthoracic and transesophageal echocardiography with color flow Doppler demonstrated a membranous VSD with left-to-right and right-to-left bidirectional shunts during ventricular systole and diastole, respectively, with an right ventricular systolic pressure of 93 mm Hg, dilation of the atria and the right ventricle, and right ventricular hypertrophy. The pulmonary valve was severely stenotic with transpulmonary valve peak velocity of 6.1 m/s and a peak pressure gradient of 147 mm Hg. The pulmonary artery and inferior vena cava were mildly dilated, and the left ventricular dimension and systolic function were normal. Transesophageal echocardiography with saline solution microbubble injection demonstrated positive contrast effect in the left ventricle in diastole confirming a right-to-left shunt at the ventricular level. This man is currently the oldest survivor with a moderate-to-large-sized membranous VSD reported in the literature.

Aged↗

PubMed1996

Total Synthesis of (-)- and (+)-Balanol(1).

Two total syntheses of the potent protein kinase C inhibitory fungal metabolite balanol are described. In the first approach, the core aminohydroxyazepane subunit was prepared in racemic form by stereospecific functionalization of N-benzyl-epsilon-caprolactam. Resolution prior to coupling to the benzophenone subunit provided access to both enantiomers of balanol. In the second approach, an efficient silicon-mediated cyclization of (2S,3R)-3-hydroxylysine followed by reduction provided the azepane subunit in enantiomerically pure form. The sterically congested benzophenone subunit was assembled from two highly substituted aromatic precursors by way of an anionic homo-Fries rearrangement.

Journal Article↗

PubMedDate not supplied

Automated analysis of proton NMR spectra from combinatorial rapid parallel synthesis using self-organizing maps.

It is now quite routine to acquire proton NMR spectra of compounds in 96-well plates prepared in a rapid parallel synthesis fashion using a flow-NMR automation setup. However, the analysis of 96 NMR spectra obtained in this manner is often laborious and painstakingly slow. We have developed a new, automated method for rapidly analyzing 96 NMR spectra of compounds synthesized in an 8 x 12 matrix using self-organizing maps (SOM). This unsupervised neural network is capable of clustering together NMR spectra containing a common pattern of -R groups and identifying outliers from within such clusters. Analysis of these outlier spectra can quickly help indicate the presence of undesired products, impurities, starting materials, and other unexpected errors in a 96-well plate synthesis by focusing the chemists' attention on the aberrant NMR spectra. Thus, SOM can be a valuable tool in performing efficient quality control on combinatorial libraries.

Combinatorial Chemistry Techniques↗