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

Maralinganadoddi P. Sadashiva, Raghavendra Gowda, Xianzhu Wu, Gajanan S. Inamdar, Omer Kuzu, Kanchugarakoppal S. Rangappa, Gavin P. Robertson, D. Channe Gowda

Research output: Contribution to journalArticle

11 Citations (Scopus)

Abstract

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 μM. Interestingly, N-dehydroabietylbenzamide showed potent antimalarial activity (IC50 0.36), and negligible cytotoxicity (IC50 >100μM) 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 ~82 μM. Several carboxylic group-derivatives of abietic acid were moderately active with IC50 values of ~8.2 to ~13.3.μM. 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.

Original languageEnglish
Pages (from-to)68-73
Number of pages6
JournalExperimental Parasitology
Volume155
DOIs
Publication statusPublished - 1 Aug 2015
Externally publishedYes

Fingerprint

Antimalarials
Inhibitory Concentration 50
Parasites
Diterpenes
Malaria
Abietane Diterpenes
Plasmodium malariae
Structure-Activity Relationship
Drug Resistance
dehydroabietylamine
abietic acid

Keywords

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

ASJC Scopus subject areas

  • Parasitology
  • Immunology

Cite this

Sadashiva, M. P., Gowda, R., Wu, X., Inamdar, G. S., Kuzu, O., Rangappa, K. S., ... Gowda, D. C. (2015). A non-cytotoxic N-dehydroabietylamine derivative with potent antimalarial activity. Experimental Parasitology, 155, 68-73. https://doi.org/10.1016/j.exppara.2015.05.002

A non-cytotoxic N-dehydroabietylamine derivative with potent antimalarial activity. / Sadashiva, Maralinganadoddi P.; Gowda, Raghavendra; Wu, Xianzhu; Inamdar, Gajanan S.; Kuzu, Omer; Rangappa, Kanchugarakoppal S.; Robertson, Gavin P.; Gowda, D. Channe.

In: Experimental Parasitology, Vol. 155, 01.08.2015, p. 68-73.

Research output: Contribution to journalArticle

Sadashiva, MP, Gowda, R, Wu, X, Inamdar, GS, Kuzu, O, Rangappa, KS, Robertson, GP & Gowda, DC 2015, 'A non-cytotoxic N-dehydroabietylamine derivative with potent antimalarial activity', Experimental Parasitology, vol. 155, pp. 68-73. https://doi.org/10.1016/j.exppara.2015.05.002
Sadashiva, Maralinganadoddi P. ; Gowda, Raghavendra ; Wu, Xianzhu ; Inamdar, Gajanan S. ; Kuzu, Omer ; Rangappa, Kanchugarakoppal S. ; Robertson, Gavin P. ; Gowda, D. Channe. / A non-cytotoxic N-dehydroabietylamine derivative with potent antimalarial activity. In: Experimental Parasitology. 2015 ; Vol. 155. pp. 68-73.
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