Preparation and biological evaluation of ethionamide-mesoporous silicon nanoparticles against Mycobacterium tuberculosis

: Vale N, Correia A, Silva S, Figueiredo P, Makila E, Salonen J, Hirvonen J, Pedrosa J, Santos HA, Fraga A

Publisher: PERGAMON-ELSEVIER SCIENCE LTD

: 2017

: Bioorganic and Medicinal Chemistry Letters

: BIOORGANIC & MEDICINAL CHEMISTRY LETTERS

: BIOORG MED CHEM LETT

: 27

: 3

: 403

: 405

: 3

: 0960-894X

DOI: https://doi.org/10.1016/j.bmcl.2016.12.060

Ethionamide (ETH) is an important second-line antituberculosis drug used for the treatment of patients infected with multidrug-resistant Mycobacterium tuberculosis. Recently, we reported that the loading of ETH into thermally carbonized-porous silicon (TCPSi) nanoparticles enhanced the solubility and permeability of ETH at different pH-values and also increased its metabolization process. Based on these results, we synthesized carboxylic acid functionalized thermally hydrocarbonized porous silicon nanoparticles (UnTHCPSi NPs) conjugated with ETH and its antimicrobial effect was evaluated against Mycobacterium tuberculosis strain H37Rv. The activity of the conjugate was increased when compared to free-ETH, which suggests that the nature of the synergy between the NPs and ETH is likely due to the weakening of the bacterial cell wall that improves conjugate-penetration. These ETH-conjugated NPs have great potential in reducing dosing frequency of ETH in the treatment of multidrug-resistant tuberculosis (MDR-TB). (C) 2016 Elsevier Ltd. All rights reserved.