Biancolino Marino, L.(Leonardo)

Filtering

20171

Settings

Author search.filters.isAuthorOfPublication.ffd847ee-3792-434c-8a70-29f30237575b

Search Results

Now showing 1 - 1 of 1
  • Thumbnail Image
    Design, Synthesis and Characterization of N-oxide-containing Heterocycles with In vivo Sterilizing Antitubercular Activity
    (2017-10) Maringolo-Ribeiro, C.(Camila); Dos-Santos, J.L.(Jean Leandro); Wang, Y.(Yuehong); Franzblau, S.G. (Scott G.); Bento-da-Silva, P.(Patricia); De-Souza-Costa, C.A. (Carlos Alberto); Lazzarato, L. (Loretta); Chegaev, K. (Konstantin); Pérez-Silanes, S. (Silvia); Pavan, F.R.(Fernando Rogério); Paucar, R. (Rocío); Man-Chin, C.(Chung); Biancolino Marino, L.(Leonardo); Hunt, D.M.(Debbie M.); Guglielmo, S. (Stefano); De-Carvalho, L.P.S. (Luiz Pedro S.); Paiva Silva, C.S (Caio Sander); De-Souza, P.C (Paula Carolina); Cho, S.H. (Sang-Hyun); Moreno-de-Viguri, E. (Elsa); Longhin Bosquesi, P. (Priscila); Santivañez-Veliz, M. (Mery); Dos-Santos-Fernandes, G.F. (Guilherme-Felipe); Solcia, M.C. (María Cristina); Chorilli, M.(Marlus); Fruttero, R. (Roberta)
    Tuberculosis, caused by the Mycobacterium tuberculosis (Mtb), is the infectious disease responsible for the highest number of deaths worldwide. Herein, 22 new N-oxide- containing compounds were synthesized followed by in vitro and in vivo evaluation of their antitubercular potential against Mtb. Compound 8 was found to be the most promising compound, with MIC90 values of 1.10 and 6.62 μM against active and non- replicating Mtb, respectively. Additionally, we carried out in vivo experiments to confirm the safety and efficacy of compound 8; the compound was found to be orally bioavailable and highly effective leading to the reduction of the number of Mtb to undetected levels in a mouse model of infection. Microarray-based initial studies on the mechanism of action suggest that compound 8 blocks the process of translation. Altogether, these results indicated benzofuroxan derivative 8 to be a promising lead compound for the development of a novel chemical class of antitubercular drugs.