Gallinamide A is potent and selective inhibitor of the human cysteine protease Cathepsin L1 that was first used as a moderate antimalarial agent. Gallinamide A is produced by marine cyanobacteria from Schizothrix species and Symploca sp.Joshawna K Nunnery, Emily Mevers, William H Gerwick, Biologically active secondary metabolites from marine cyanobacteria, Current Opinion in Biotechnology, Volume 21, Issue 6, 2010, Pages 787-793, ISSN 0958-1669, which have also shown to have possible anticancer agent, infectious diseases like leishmaniasis, trypanosomiasis and possible uses in Alzheimer's disease, among others.
History Gallinamide A was first isolated from a Panamanian collection of marine cyanobacteria in 2009 (Schizothrix species) for activity against the malaria causing parasite Plasmodium falciparum. Later, was subsequently and independently isolated by Taori and co-workers from a Floridian Cyanobacteria collection in Key Largo from Symploca sp. and given the name symplostatin 4. Gallinamide A, among other cyanobacteria metabolites such as viridamide A & B, dragonamide E, and almiramide E; are lipodepsipeptides that proved to show anti-infective activities. Gallinamide A was originally isolated with a modest antimalarial activity, which was then proven to be a potent inhibitor of cysteine protease cathepsin L with a IC50 5.0 ug/mL, nonetheless, human cathepsin L is involved in many diseases, gallinamide A was tested in HeLa cervical cancer cells with a IC50 12 mM and in HT-29 colon adenocarcinoma cells with an IC50 of mM.
Mechanism of action Gallinamide A is a potent and selective irreversible inhibitor of human Cathepsin L1, with a high selectivity towards cysteine cathepsin protease family.
Total synthesis The first stereoselective synthesis was reported by Conroy and co-workers.
Clinical study Gallinamide A is a potent inhibitor of cathepsin L with an IC50 value of 17.6 pM. Also, was tested for its antimalarial activity against the W2 chloroquine-resistant strain of the malaria parasite. This compound showed moderate in vitro activity against Plasmodium falciparum (IC50 = 8.4 μM), cytotoxicity to mammalian Vero cells (TC50 = 10.4 μM) and activity against Leishmania donovani of (IC50 = 9.3 μM), but was inactive up to the highest tested concentrations against Trypanasoma cruzi (16.9 μM). No in vivo or human testing has been perform since it is only for research development.
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