No abstract

Metalloproteins have attracted momentous attentions for the treatment of many human diseases, including cancer, HIV, hypertension, etc. This article reviews the progresses that have been made in the field of drug development of metalloprotein inhibitors, putting emphasis on the targets of carbonic anhydrase, histone deacetylase, angiotensin converting enzyme, and HIV-1 integrase. Many other important metalloproteins are also briefly discussed. The binding and coordination modes of different marketed metalloprotein inhibitors are stated, providing insights to design novel metal binding groups and further novel inhibitors for metalloproteins.

A phenotypic screen of a diverse library of small molecules for inhibition of the development of larvae of the parasitic nematode Haemonchus contortus led to the identification of a 1-methyl-1H-pyrazole-5-carboxamide derivative with an IC 50 of 0.29 μM. Medicinal chemistry optimization targeted modifications on the left-hand side (LHS), middle section, and right-hand side (RHS) of the scaffold in order to elucidate the structure−activity relationship (SAR). Strong SAR allowed for the iterative and directed assembly of a focus set of 64 analogues, from which compound 60 was identified as the most potent compound, inhibiting the development of the fourth larval (L4) stage with an IC 50 of 0.01 μM. In contrast, only 18% inhibition of the mammary epithelial cell line MCF10A viability was observed, even at concentrations as high as 50 μM.

A new isoflavone, corylinin (1), along with six known compounds, isopsoralen (2), psoralen (3), sophoracoumestan A (4), neobavaisoflavone (5), daidzin (6) and uracil (7), have been isolated from the dried fruits of Psoralea corylifolia L. The structure of 1 was established as 7,4'-dihydroxy-3'-[(E)-3,7-dimethyl-2,6-octadienyl]isoflavone on the basis of the spectroscopic methods. Structures of the known compounds were identified by comparison of the literature.