Design, Synthesis, and Biological Evaluation of Isothiosemicarbazones with Antimycobacterial Activity. Issue 8 (21st June 2017)

• Record Type: Journal Article
• Authors: Novotná, Eva; Waisser, Karel; Kuneš, Jiří; Palát, Karel; Skálová, Lenka; Szotáková, Barbora; Buchta, Vladimír; Stolaříková, Jiřina; Ulmann, Vít; Pávová, Marcela; Weber, Jan; Komrsková, Jitka; Hašková, Pavlína; Vokřál, Ivan; Wsól, Vladimír
• Is Part Of: Archiv der Pharmazie. Volume 350:Issue 8(2017)
• Page Start: n/a
• Page End: n/a
• Publication Date: 2017-06-21
• Subjects: Biological activity -- Cytotoxicity -- Isocitrate lyase -- Isothiosemicarbazone -- Tuberculosis; Pharmaceutical chemistry -- Periodicals; Pharmacology -- Periodicals; 615.19
• DOI: 10.1002/ardp.201700020
• Languages: English
• ISSNs: 0365-6233

Abstract

Abstract : 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 μmol/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. Abstract : A series of benzaldehyde and salicylaldehyde‐ S ‐benzylisothiosemicarbazones was synthesized and tested for antimycobacterial selectivity. Twenty‐eight derivatives were evaluated for the inhibition of isocitrate lyase, a key enzyme of the glyoxylate cycle necessary for latent tuberculosis infection. The compounds show promising activity as potential antibiotics with the main effect on mycobacteria.