Computer-aided study of the relationship between structure and antituberculosis activity of a series of isoniazid derivatives Original Research Article

The Multiple Computer Automated Structure Evaluation (MultiCASE) program was used to analyze the relationship between the structure and antituberculous activity of a series of 136 hydrazides, most of them isoniazid related. The structural features revealed by this analysis are discussed. The most significant one seemed to be the distance between the pyridinic nitrogen and the terminal nitrogen of the hydrazido group. Given the affiliation of these two heteroatoms with a planar conjugated system, we suggest that Schiff base chemistry similar to that of vitamin B6 may be involved in the mode of action of isoniazid and its related compounds. A mechanism of action of isoniazid is proposed and suggestions for the design of new isoniazid-type drugs are made.