Synthesis and antituberculosis activity of indole-pyridine derived hydrazides, hydrazide-hydrazones, and thiosemicarbazones.

ABSTRACT

We describe the design, synthesis, and in vitro antimycobacterial activity of a series of novel simple hybrid hydrazides and hydrazide-hydrazones combining indole and pyridine nuclei. The compounds are derivatives of 1-acetylindoxyl or substituted indole-3-carboxaldehydes tethered via a hydrazine group by simple C-N or double C=N bonds with 3- and 4-pyridines, 1-oxide 3- and 4-pyridine carbohydrazides. The most active of 15 compounds showed MICs values against an INH-sensitive strain of Mycobacterium tuberculosis H37Rv equal to that of INH (0.05-2 µg/mL). Five compounds demonstrated appreciable activity against the INH-resistant M. tuberculosis CN-40 clinical isolate (MICs 2-5 µg/mL), providing justification for further in vivo studies.