A non-cytotoxic N-dehydroabietylamine derivative with potent antimalarial activity

作者：Sadashiva Maralinganadoddi P^*; Gowda Raghavendra; Wu Xianzhu; Inamdar Gajanan S; Kuzu Omer F; Rangappa Kanchugarakoppal S; Robertson Gavin P; Gowda D Channe

来源：Experimental Parasitology, 2015, 155: 68-73.

DOI：10.1016/j.exppara.2015.05.002

• Abietane diterpenoids
• Dehydroabietylamine derivatives
• Abietic acid derivatives
• Antimalarial activity

Malaria caused by the Plasmodium parasites continues to be an enormous global health problem owing to wide spread drug resistance of parasites to many of the available antimalarial drugs. Therefore, development of new classes of antimalarial agents is essential to effectively treat malaria. In this study, the efficacy of naturally occurring diterpenoids, dehydroabietylamine and abietic acid, and their synthetic derivatives was assessed for antimalarial activity. Dehydroabietylamine and its N-trifluoroacetyl, N-tribromoacetyl, N-benzoyl, and N-benzyl derivatives showed excellent activity against P. falciparum parasites with IC50 values of 0.36 to 2.6 mu M. Interestingly, N-dehydroabietylbenzamide showed potent antimalarial activity (IC50 0.36), and negligible cytotoxicity (IC50 >100 mu M) to mammalian cells; thus, this compound can be an important antimalarial drug. In contrast, abietic acid was only marginally effective, exhibiting an IC50 value of similar to 82 mu M. Several carboxylic group-derivatives of abietic acid were moderately active with IC50 values of similar to 8.2 to similar to 13.3 mu M. These results suggest that a detailed understanding of the structure-activity relationship of abietane diterpenoids might provide strategies to exploit this class of compounds for malaria treatment.

• 出版日期2015-8