Allylic thiocyanates as a new class of antitubercular agents.

Abstract TB is a global public health emergency in which new drugs are desperately needed. Herein we report on the synthesis of a diverse panel of 41 aryl allylic azides, thiocyanates, isothiouronium salts, and N , N ′-diacetylisothioureas that were evaluated for their in vitro activity against replicating and non-replicating Mycobacterium tuberculosis ( Mtb ) H 37 Rv and toxicity to VERO cells. We found a selective group of new and promising compounds having good (micromolar) to excellent (sub-micromolar) potency against replicating Mtb H 37 Rv. Allylic thiocyanates bearing halophenyl (halo = 2-Br, 4-Br, 4-Cl, 4-F), 4-methylphenyl and 2-naphthyl moieties were the most active as antitubercular agents. In particular, the 2-bromophenyl-substituted thiocyanate showed MIC = 0.25 μM against replicating Mtb , MIC = 8.0 μM against non-replicating Mtb and IC 50  = 32 μM in the VERO cellular toxicity assay.