Synthesis of isonicotinoylhydrazones from anacardic acid and their in vitro activity against Mycobacterium smegmatis

Isonicotinoylhydrazones were synthesized from a natural product anacardic acid, a major constituent of cashew nut shell liquid. The unsaturated side chain in anacardic acid and its 5-nitro derivative were converted into C8′-aldehydes by oxidative cleavage. C8′-aldehydes are then coupled with isoniazid (an anti-TB drug) to obtain N-isonicotinoyl-N′-8-[(2′-carbohydroxy-3′-hydroxy) phenyl] octanal hydrazone (5) and N-isonicotinoyl-N′-8-[(2′-carbohydroxy-3′-hydroxy-6-nitro) phenyl] octanal hydrazone (6). These isonicotinoylhydrazones of anacardic aldehydes showed potent antimycobacterial activity against Mycobacterium smegmatis mc2155. The synergistic studies of 5 and 6 with isoniazid showed more inhibitory activities than isoniazid alone. Compounds 5 and 6 also showed activity against Mycobacterium tuberculosis H37Rv.

Graphical abstract The synthesis of novel isonicotinoylhydrazones (5 and 6) from a natural product anacardic acid is reported. These compounds have been shown to possess synergistic activity against Mycobacterium smegmatis mc2155 when tested in combination with isoniazid.Figure optionsDownload full-size imageDownload as PowerPoint slide