European Society of Mycobacteriology - Instituto Nacional de Saúde ...

PP-111
ANTI-MYCOBACTERIUM TUBERCULOSIS ACTIVITY OF
THIOSEMICARBAZONES, SEMICARBAZONES AND HYDRAZONES
Leite; Sergio 1 , Pavan; Fernando 2 , Maia; Pedro 3 , Deflon; Victor 3 , Batista; Alzir 4 , Sato; Daisy 5 , Franzblau; Scott 6 , Leite; Clarice 2
1 - Universidade Estadual Paulista, Instituto de Química
2 - Universidade Estadual Paulista, Faculdade de Ciências Farmacêuticas
3 - Universidade de São Paulo, Instituto de Química de São Carlos
4 - Universidade Federal de São Carlos, Departamento de Química
5 - Instituto Adolfo Lutz, Unidade de Ribeirão Preto
6 - University of Illinois at Chicago, College of Pharmacy
The aim of this study was to identify a candidate drug for anti-tuberculosis therapy development from previously synthesized
thiosemicarbazones, semicarbazones and hydrazones, comprising a total of 17 compounds. The Minimal Inhibitory
Concentration (MIC) of these compounds, determined by the resazurin reduction method, was investigated in order to
determine their in vitro antimycobacterial activity against Mycobacterium tuberculosis. In vitro cytotoxicity values (IC50)
of the same compounds were determined on J774 cells to establish a selectivity index (SI = IC50/MIC). Lower values of
MIC were found for four thiosemicarbazones and four hydrazones, namely: 2-acetylpyridine N4 (etil) thiosemicarbazone;
2-acetylpyridine N4 (cyclohexyl) thiosemicarbazone; di-2-pyridyl ketone N4 (phenyl) thiosemicarbazone; 2-acetylpyridine
morpholyl thiosemicarbazone; mono benzoylacetone isonicotinoyl hydrazone; mono-acetylacetone isonicotinoyl hydrazone;
di-2-pyridyl ketone isonicotinoyl hidrazone; di-2-pyridyl ketone thiophene hidrazone (MIC values ranging from 0.78
to 6.25 μg/mL). All the compounds presented very low cytotoxicity, with the exception of 2-acetylpyridine morpholyl
thiosemicarbazone (IC50 ≤ 3.9 μg/mL and SI ≤ 5). The results obtained with the other 7 compounds (SI ranging from 100
to 800) qualify them as candidates for anti-TB drugs, once their in vitro results are comparable to some of “first line” and
“second line” drugs commonly used in the TB treatment.
European Society of Mycobacteriology | 30 th Annual Congress | July 2009 | Porto - Portugal
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