Exploring Anti-Leishmanial Almiramide Structure-aActivity Relationships

Leishmaniasis is a protozoan disease, which occurs in 12 to 15 million people worldwide and infects greater than 1 million new cases annually.¹ The limitations in availability of effective drugs and the rise of drug resistant strains has created an urgent need for new anti-leishmanial therapy.² In the light of the limitations of contemporary leishmaniasis therapy, the N-methylated almiramide lipo-peptides represent promising leads due to relatively high anti-leishmanial activity and low host toxicity due to theirs likely mechanism of action involving disruption of the vital energy machinery proteins of the glycosome.^3,4 With a focus on the influences of N-methylation and conformation on the antiprotozoan activity, our presentation provides a structure-activity relationship study of the almiramide peptides employing resistant parasite strains and murine macrophages.

References

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3. Sanchez, L. M.; Lopez, D.; Vesely, B. A.; Della Togna, G.; Gerwick, W. H.; Kyle, D. E.; Linington, R. G., Almiramides A− C: discovery and development of a new class of leishmaniasis lead compounds. J. Med. Chem. 2010, 53 (10), 4187-4197.
4. Sanchez, L. M.; Knudsen, G. M.; Helbig, C.; De Muylder, G.; Mascuch, S. M.; Mackey, Z. B.; Gerwick, L.; Clayton, C.; McKerrow, J. H.; Linington, R. G. Examination of the mode of action of the almiramide family of natural products against the kinetoplastid parasite Trypanosoma brucei. J. Nat. Prod. 2013, 76 (4), 630-641.