<strong>QSAR Models and Virtual Screening for Discovery of New Analgesic Leads</strong>

Abstract

The search for new selective pharmacological agents with no significant side-effects is an increasing requirement for the development of new drugs to be used in the treatment of acute and chronic pain. In the present study, a new series of compounds (VAM 1,6,10,11, 12, 24) has been screening in QSARLDA mathematic models and pharmacologically evaluated. The antinociceptive properties of the new analgesic candidates obtained of virtual screening have been investigated in vitro tests. The pre-treatment with the compounds VAM 1, 2-4, 6, 10, 11, 12, showed a potent inhibition of IL-6 on RAW cells. The blocking efficacy of nineteen compounds on several isoforms of voltage-dependent sodium channels, expressed in Xenopus laevis oocytes, was tested (Nav1.3, Nav1.5, Nav1.6, Nav1.7, and Nav1.8). An exception was Nav1.6, where VAM 24 compound to result in substantial block indicating that acts specifically at this peculiar isoform. Compounds VAM 10 and VAM 2-4 are the most potent antinociceptive agents. These results indicate the potential of the compound VAM 2-4 to treat pain conditions.