Learn More
Tuberculosis (TB) is more prevalent in the world today than at any other time in human history. Mycobacterium tuberculosis, the pathogen responsible for TB, uses diverse strategies to survive in a variety of host lesions and to evade immune surveillance. A key question is how robust are our approaches to discovering new TB drugs, and what measures could be(More)
In our efforts to find new active tyrosinase inhibitors for skin-whitening or antibrowning preparations, we investigated 67 tropical plants belonging to 38 families, which were evaluated for their anti-tyrosinase activity. The results of our investigation show that extracts of 5 plants, Stryphnodendron barbatimao, Portulaca pilosa, Cariniana brasiliensis,(More)
We previously reported the discovery of substituted benzimidazole fusion inhibitors with nanomolar activity against respiratory syncytial virus (Andries, K.; et al. Antiviral Res. 2003, 60, 209-219). A lead compound of the series was selected for preclinical evaluation. This drug candidate, JNJ-2408068 (formerly R170591, 1), showed long tissue retention(More)
Six-helix bundle (6HB) formation is an essential step for many viruses that rely on a class I fusion protein to enter a target cell and initiate replication. Because the binding modes of small molecule inhibitors of 6HB formation are largely unknown, precisely how they disrupt 6HB formation remains unclear, and structure-based design of improved inhibitors(More)
The genome of all retroviruses consists of two identical copies of an RNA sequence associated in a non-covalent dimer. A region upstream from the splice donor (SL1) comprising a self-complementary sequence is responsible for the initiation of the dimerization. This region is able to dimerize in two conformations: a loop-loop complex or an extended duplex.(More)
Respiratory syncytial virus (RSV) is a leading cause of pneumonia and bronchiolitis in young children and the elderly. Therapeutic small molecules have been developed that bind the RSV F glycoprotein and inhibit membrane fusion, yet their binding sites and molecular mechanisms of action remain largely unknown. Here we show that these inhibitors bind to a(More)
This paper reports the synthesis and antiviral properties of new difluoromethylbenzoxazole (DFMB) pyrimidine thioether derivatives as non-nucleoside HIV-1 reverse transcriptase inhibitors. By use of a combination of structural biology study and traditional medicinal chemistry, several members of this novel class were synthesized using a single electron(More)
  • 1