The present invention relates to methods of modulating activity of histone deacetylases (HDACs). The present invention also relates to methods of treating HDAC-associated diseases including, but not limited to, cancers, inflammatory disorders, and neurodegenerative disorders. The present invention also provides novel compounds and compositions thereof and methods of preparation of the same. The present invention also includes methods of inhibiting HDACs, and methods of treating HDAC-associated diseases using the compounds of the invention.