Synthesis and biological evaluation of tricyclic guanidine analogues of batzelladine K for antimalarial, antileishmanial, antibacterial, antifungal, and anti-HIV activities

Abstract

Fifty analogues of batzelladine K were synthesized and evaluated for in vitro antimalarial (Plasmodium falciparum), antileishmanial (Leishmania donovani), antimicrobial (panel of bacteria and fungi), antiviral (HIV-1) activities. Analogues 14h and 20l exhibited potential antimalarial activity against chloroquine-sensitive D6 strain with IC₅₀ 1.25 and 0.88 μm and chloroquine-resistant W2 strain with IC₅₀ 1.64 and 1.07 μm, respectively. Analogues 12c and 14c having nonyl substitution showed the most potent antileishmanial activity with IC₅₀ 2.39 and 2.78 μm and IC₉₀ 11.27 and 12.76 μm, respectively. Three analogues 12c, 14c, and 14i were the most active against various pathogenic bacteria and fungi with IC₅₀ < 3.02 μm and MIC/MBC/MFC <6 μm. Analogue 20l having pentyl and methyl substituents on tricycle showed promising activities against all pathogens. However, none was found active against HIV-1. Our study demonstrated that the tricyclic guanidine compounds provide new structural class for broad spectrum activity.