Design, Synthesis, and Biological Evaluation of Isothiosemicarbazones with Antimycobacterial Activity

0478148 - ÚOCHB 2018 RIV DE eng J - Článek v odborném periodiku
Novotná, E. - Waisser, K. - Kuneš, J. - Palát, K. - Skálová, L. - Szotáková, B. - Buchta, V. - Stolaříková, J. - Ulmann, V. - Pávová, Marcela - Weber, Jan - Komrsková, J. - Hašková, P. - Vokřál, I. - Wsól, V.
Design, Synthesis, and Biological Evaluation of Isothiosemicarbazones with Antimycobacterial Activity.
Archiv der Pharmazie. Roč. 350, č. 8 (2017), č. článku e1700020. ISSN 0365-6233. E-ISSN 1521-4184
Institucionální podpora: RVO:61388963
Klíčová slova: biological activity * cytotoxicity * isocitrate lyase * isothiosemicarbazone * tuberculosis
Obor OECD: Microbiology
Impakt faktor: 2.288, rok: 2017

A series of benzaldehyde and salicylaldehyde-S-benzylisothiosemicarbazones was synthesized and tested against 12 different strains of mycobacteria, Gram-positive and Gram-negative bacteria, and the significant selectivity toward mycobacteria was proved. Twenty-eight derivatives were evaluated for the inhibition of isocitrate lyase, which is a key enzyme of the glyoxylate cycle necessary for latent tuberculosis infection, and their iron-chelating properties were investigated. Two derivatives, 5-bromosalicylaldehyde-S-(4-fluorobenzyl)-isothiosemicarbazone and salicylaldehyde-S-(4-bromobenzyl)-isothiosemicarbazone, influenced the isocitrate lyase activity and caused a better inhibition at 10 mu mol/L than 3-nitropropionic acid, a standard inhibitor. The compounds were also found to act as exogenous chelators of iron, which is an obligate cofactor for many mycobacterial enzymes. Due to their low cytotoxicity, together with the activity against isocitrate lyase and the ability to sequester iron ions, the compounds belong to potential antibiotics with the main effect on mycobacteria.
Trvalý link: http://hdl.handle.net/11104/0274348