Trypanocidal 1,3-arylene diketone bis(guanylhydrazones). Structure-activity relationships among substituted and heterocyclic analogs

Publisher Website
Google Scholar
Abstract
Based on the antitrypanosomal activity of 1,3-diacetylbenzene bis(guanylhydrazone) (4) and 2,6-diacetylpyridine bis(guanylhydrazone) (17), a number of substituted and heterocyclic 1,3-arylene diketone bis(guanylhydrazone)s were prepared and tested against Trypanosoma brucei infections in mice. A wide range of ED50 [50% of the effective dose] values was observed among 5-substituted derivatives of 4. The 5-amino analog (5) and 5-acetamido analog were about twice as active as 4. 1,3,5-Triacetylbenzene tris(guanylhydrazone) was about 9 times as active as 4 and was about as active as the currently used trypanocide diminazene aceturate in this test system. Other 5 derivatives had activity equivalent to or less than that of the parent compound 4. Three new heterocyclic analogs were all less active than 2,6-diacetylpyridine derivative and benzene derivative 4. Ring substitution ortho to the guanylhydrazone side chains was invariably detrimental to activity. Side-chain homologues 1,3-dipentanoylbenzene bis(guanylhydrazone) and 1,3-diacetylbenzene bis(2-imidazolin-2-ylhydrazone) were essentially inactive.