Design, structural and spectroscopic elucidation of new nitroaromatic carboxylic acids and semicarbazones for the in vitro screening of anti-leishmanial activity

• Published in: Journal of molecular structure 2015-01, Vol.1079, p.298-306
• Main Authors: Dias, L.C., de Lima, G.M., Pinheiro, C.B., Rodrigues, B.L., Donnici, C.L., Fujiwara, R.T., Bartholomeu, D.C., Ferreira, R.A., Ferreira, S.R., Mendes, T.A.O., da Silva, J.G., Alves, M.R.A.
• Format: Article
• Language: English
• Subjects: Anti-leishmanial activity; Carboxylic acids; Diffraction; Drugs; In vitro testing; Infrared; Leishmania infantum; Molecular structure; Nitroaromatic compounds; NMR spectroscopy; Semicarbazones; Side effects; Veterinary
• ISSN: 0022-2860; 1872-8014
• DOI: 10.1016/j.molstruc.2014.08.047

•Four new nitroaromatic carboxylic acids and semicarbazones have been prepared and fully characterized.•Compound (3) was the most efficient with an IC50 value of 3.0μmolL−1.•Compound (3) might be effective as a veterinary anti-leishmania agent.•Reduction of Ar–NO2 into Ar–NO2− is vital for the biocide activity of (1)–(4). In this paper we report the synthesis and characterization of four new nitroaromatic compounds, 2-{6-nitrobenzo[1,3]dioxol-5-(methyleneamino)}benzoic acid (1), 2-{[5-(2-nitrophenyl)furan-2-yl]methylene-amino}benzoic acid (2), 2-{(6-nitrobenzo[1,3]dioxol-5-yl)methylene}hydrazinecarboxamide (3) and 2-{[5-(2-nitrophenyl)furan-2-yl]methylene}hydrazinecarboxamide (4). Compounds (1)–(4) have been authenticated by infrared and NMR spectroscopy, and the structure of (1), (2) and (4) have been determined by X-ray diffraction. In addition, the in vitro ability of compounds (1)–(4) to inhibit the growth of Leishmania infantum has been evaluated. Comparisons of the redox potential of the compounds and leishmanicidal activity indicate that the presence of the electroactive nitro group is important for the biological activity. The inhibition activity of compound (3) is comparable to that of the reference drug, SbCl3. Considering the important side effects and the low efficiency of SbCl3 in the case of resistance, compound (3) deserves further attention as a promising anti-leishmanicidal drug for veterinary use.