Английская Википедия:Gallinamide A
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.[1] which have also shown to have possible anticancer agent, infectious diseases like leishmaniasis, trypanosomiasis and possible uses in Alzheimer's disease, among others.[2]
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.[3] 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.[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.[3] 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,[2] 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.[1]
Total synthesis
The first stereoselective synthesis was reported by Conroy and co-workers.[3]
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.[4]
References
External links
- Gallinamide A https://www.medchemexpress.com/gallinamide-a.html
- ↑ 1,0 1,1 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,
- ↑ 2,0 2,1 Шаблон:Cite journal
- ↑ 3,0 3,1 3,2 Шаблон:Cite journal
- ↑ 4,0 4,1 Шаблон:Cite journal
