Synthesis and biological evaluation of 9-aryl-1,8-dioxo-octahydroxanthene derivatives as antileishmanial agents

In the current research, we designed and synthesized various derivatives of 9-aryl-1,8-dioxo-octahydroxanthene using flow chemistry technique and explored in vitro study for antileishmanial activity against the promastigote as well as amastigote form of Leishmania donovani strain. Among the tested analogs by various cell viability assays, six compounds exhibited antileishmanial activity with IC50 value ranging from 24.81 to 52.33 mu M. Further, the functional dynamics study sheds light on the structural role of various functional groups presents in the xanthene derivatives for defining the actual antileishmanial activity. Molecular dynamics simulation data presented here attempts to provide a structural and mechanistic explanation of threonine synthase inhibition against Leishmania donovani by xanthene derivatives. Described structure-activity-relation advocates for further modification of the xanthene scaffolds for the accomplishment of challenging antileishmanial drugs.

Automated summary

In this research, we synthesized various derivatives of 9-aryl-1,8-dioxo-octahydroxanthene using flow chemistry technique and tested their antileishmanial activity against Leishmania donovani strain. Six compounds exhibited antileishmanial activity with IC50 values ranging from 24.81 to 52.33 μ M. Molecular dynamics simulation data provided a structural and mechanistic explanation for threonine synthase inhibition against Leishmania donovani by xanthene derivatives. The study suggests further modification of the xanthene scaffolds for the development of effective antileishmanial drugs.