In vitro antileishmanial effects of antibacterial diterpenes from two Ethiopian Premna species: P. schimperi and P. oligotricha

Abstract

Background

Three antibacterial diterpenes: (5R,8R,9S,10R)-12-oxo-ent-3,13(16)-clerodien-15-oic acid ( 1), 16-hydroxy-clerod-3,13(14)-diene-15,16-olide ( 2) and ent-12-oxolabda-8,13(16)-dien-15-oic acid ( 3) were previously isolated form Premna schimperi and P. oligotricha. Since andrographolide and other structurally related diterpenes were shown to have antileishmanial activity, the aim of the present study was to assess the in vitro effect of premna diterpenes against Leishmania aethiopica; the causative agent of cutaneous leishmaniasis in Ethiopia.

Results

The diterpenes showed potent concentration-dependant suppressive effect on the viability of axenically cultured amastigotes of L. aethiopica. The clerodane diterpenes 1 and 2 were most active (LD ₅₀ values 1.08 and 4.12 μg/ml respectively) followed by andrographolide and 3. Compounds 1 and 2 appear to be over 20 and 10-times respectively more selective to leishmania amastigotes than the permissive host cell line, THP-1 cells or the promastigotes stage of the parasites.

Conclusion

The clerodane diterpenes ( 1, 2) which were more potent and selective than labdanes (andrographolide and 3) are promising for further studies and/or development.