Affiliation: Faculty of Pharmacy in Hradec Kralove, Charles University in Prague, Heyrovskeho 1203, 500 05 Hradec Kralove, Czech Republic.
Tuberculosis remains the leading cause of mortality worldwide even in the 21st century. This review summarises all facts concerning a front-line antituberculotic drug isoniazide – metabolism, mechanism of activity and resistance. The antimycobacterial pharmacophore moiety of isoniazide has been introduced in a number of various types of molecules (about 510 derivatives have been found) to improve their activity against Mycobacteria species, as well as their multidrug-resistant strains. Several Schiff bases, hydrazones, hydrazides and metal complexes of isoniazide have shown very good activity. Various types of the most active isoniazide derivatives classified according to their structure are reported, their lipophilicity has been calculated and structure-activity relationships are discussed. The original new highly active isoniazide prodrug forms prepared at the Faculty of Pharmacy, Charles University, Czech Republic are presented in a separate chapter of the paper.