Chemistry:Gallinamide A
| |
| Identifiers | |
|---|---|
3D model (JSmol)
|
|
| ChEMBL | |
| ChemSpider | |
PubChem CID
|
|
| |
| |
| Properties | |
| C31H52N4O7 | |
| Molar mass | 592.778 g·mol−1 |
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa). | |
 verify (what is   ?)
| |
| Infobox references | |
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
- ↑ 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 Boudreau, Paul D.; Miller, Bailey W.; McCall, Laura-Isobel; Almaliti, Jehad; Reher, Raphael; Hirata, Ken; Le, Thu; Siqueira-Neto, Jair L. et al. (24 October 2019). "Design of Gallinamide A Analogs as Potent Inhibitors of the Cysteine Proteases Human Cathepsin L and Trypanosoma cruzi Cruzain". Journal of Medicinal Chemistry 62 (20): 9026–9044. doi:10.1021/acs.jmedchem.9b00294. PMID 31539239.
- ↑ 3.0 3.1 3.2 Conroy, Trent; Guo, Jin T.; Elias, Nabiha; Cergol, Katie M.; Gut, Jiri; Legac, Jennifer; Khatoon, Lubna; Liu, Yang et al. (26 December 2014). "Synthesis of Gallinamide A Analogues as Potent Falcipain Inhibitors and Antimalarials". Journal of Medicinal Chemistry 57 (24): 10557–10563. doi:10.1021/jm501439w. PMID 25412465.
- ↑ 4.0 4.1 Miller, Bailey; Friedman, Aaron J.; Choi, Hyukjae; Hogan, James; McCammon, J. Andrew; Hook, Vivian; Gerwick, William H. (24 January 2014). "The Marine Cyanobacterial Metabolite Gallinamide A Is a Potent and Selective Inhibitor of Human Cathepsin L". Journal of Natural Products 77 (1): 92–99. doi:10.1021/np400727r. PMID 24364476.
External links
- Gallinamide A https://www.medchemexpress.com/gallinamide-a.html
 |  |
