Anti-leishmanial activity of betulin derivatives

Betulin (lup-20(29)-ene-3ß,28-diol) is an abundant naturally occurring triterpene, and it is found predominantly in bushes and trees forming the principal extractive (up to 30% of dry weight) of the bark of birch trees. Betulin and its derivatives such as betulinic acid have many interesting pharmacological properties, such as cytotoxic activity against many tumour cell lines and anti-HIV activity with a new mechanism of action. Several synthetic betulin derivatives that have been chemically modified at the positions C-3 and C-28 of the lupane skeleton were produced, and the anti-leishmanial inhibition activity of compounds was evaluated at 50 µM against Leishmania donovani and Leishmania tropica. Betulonic acid had the best anti-leishmanial activity with remarkable 98% inhibition at 50 µM giving a GI50 value of 14.6 µM. In conclusion, carbonyl or carboxyl groups seem to have beneficial effect in anti-leishmanial inhibition activity, and these compounds represent important leads for further optimization