In vitro anti-mycobacterial activity of (E)-N'-(monosubstituted-benzylidene) isonicotinohydrazide derivatives against isoniazid-resistant strains.
A series of twenty-three N-acylhydrazones derived from isoniazid (INH 1-23) have been evaluated for their in vitro antibacterial activity against INH- susceptible strain of M. tuberculosis (RG500) and three INH-resistant clinical isolates (RG102, RG103 and RG113). In general, derivatives 4, 14, 15 and 16 (MIC=1.92, 1.96, 1.96 and 1.86 µM, respectively) showed relevant activities against RG500 strain, while the derivative 13 (MIC=0.98 µM) was more active than INH (MIC=1.14 µM). However, these derivatives were inactive against RGH102, which displays a mutation in the coding region of inhA. These results suggest that the activities of these compounds depend on the inhibition of this enzyme. However, the possibility of other mechanisms of action cannot be excluded, since compounds 2, 4, 6, 7, 12-17, 19, 21 and 23 showed good activities against katG-resistant strain RGH103, being more than 10-fold more active than INH.
Universidade Federal do Rio Grande, Rio Grande do Sul;
Tatiane S
TS
Coelho
Universidade Federal do Rio Grande, Rio Grande do Sul;
Jessica B
JB
Cantos
Fundação Oswaldo Cruz, Instituto de Tecnologia em Fármacos-Far Manguinhos; ; Universidade Federal do Rio de Janeiro, Instituto de Química, Departamento de Química Orgânica, RS, Brazil.
Marcelle L F
ML
Bispo
Fundação Oswaldo Cruz, Instituto de Tecnologia em Fármacos-Far Manguinhos; ; Universidade Federal do Rio de Janeiro, Instituto de Química, Departamento de Química Orgânica, RS, Brazil.
Raoni S B
RS
Gonçalves
Fundação Oswaldo Cruz, Instituto de Tecnologia em Fármacos-Far Manguinhos; ; Universidade Federal do Rio de Janeiro, Instituto de Química, Departamento de Química Orgânica, RS, Brazil.
Camilo H S
CH
Lima
Universidade Federal do Rio Grande, Rio Grande do Sul;
Pedro E A
PE
da Silva
Fundação Oswaldo Cruz, Instituto de Tecnologia em Fármacos-Far Manguinhos; ; Universidade Federal do Rio de Janeiro, Instituto de Química, Departamento de Química Orgânica, RS, Brazil.
Marcus V N
MV
Souza
INH-resistance; N-acylhydrazones; drugs.; isoniazid; tuberculosis