title: 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.
authors.affiliation: Departamento de Química, Instituto de Química, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS, Brazil.
authors.forename: Gustavo P
authors.initials: GP
authors.lastname: Silveira
authors.forename: Misael
authors.initials: M
authors.lastname: Ferreira
authors.forename: Luciano
authors.initials: L
authors.lastname: Fernandes
authors.forename: Garrett C
authors.initials: GC
authors.lastname: Moraski
authors.forename: Sanghyun
authors.initials: S
authors.lastname: Cho
authors.forename: Changhwa
authors.initials: C
authors.lastname: Hwang
authors.forename: Scott G
authors.initials: SG
authors.lastname: Franzblau
authors.forename: Marcus M
authors.initials: MM
authors.lastname: Sá
mesh_terms: D000498:Allyl Compounds / Q000737:chemistry* / Q000494:pharmacology* / Q000633:toxicity; D000818:Animals; D000995:Antitubercular Agents / Q000737:chemistry* / Q000494:pharmacology* / Q000633:toxicity; D002522:Chlorocebus aethiops; D006801:Humans; D008826:Microbial Sensitivity Tests; D009169:Mycobacterium tuberculosis / Q000187:drug effects* / Q000254:growth & development; D013861:Thiocyanates / Q000737:chemistry* / Q000494:pharmacology* / Q000633:toxicity; D014376:Tuberculosis / Q000188:drug therapy* / Q000382:microbiology; D014709:Vero Cells
chemical_list: D000498:Allyl Compounds; D000995:Antitubercular Agents; D013861:Thiocyanates; C491148:allyl thiocyanate