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Protozoal infections are still a global health problem, threatening the lives of millions of people around the world, mainly in impoverished tropical and sub‐tropical regions. Thus, in view of the lack of efficient therapies and increasing resistances against existing drugs, this study describes the antiprotozoal potential of synthetic cinnamate ester analogues and their structure‐activity relationships. In general,  Leishmania donovani  and  Trypanosoma brucei  were quite susceptible to the compounds in a structure‐dependent manner. Detailed analysis revealed a key role of the substitution pattern on the aromatic ring and a marked effect of the side chain on the activity against these two parasites. The high antileishmanial potency and remarkable selectivity of the nitro‐aromatic derivatives suggested them as promising candidates for further studies. On the other hand, the high  in vitro  potency of catechol‐type compounds against  T. brucei  could not be extrapolated to an  in vivo  mouse model.

Structure−Activity Relationships of Cinnamate Ester Analogues as Potent Antiprotozoal Agents