Synonym
Meleagrin; 6-O-Methyloxaline; (-)-Meleagrin
IUPAC/Chemical Name
(7aR,12aS,E)-3-((1H-imidazol-5-yl)methylene)-6-hydroxy-12-methoxy-7a-(2-methylbut-3-en-2-yl)-7a,12-dihydro-1H,5H-imidazo[1',2':1,2]pyrido[2,3-b]indole-2,5(3H)-dione
InChi Key
JTJJJLSLKZFEPJ-ZAYCRUKZSA-N
InChi Code
InChI=1S/C23H23N5O4/c1-5-21(2,3)22-11-18(29)20(31)27-17(10-14-12-24-13-25-14)19(30)26-23(22,27)28(32-4)16-9-7-6-8-15(16)22/h5-13,29H,1H2,2-4H3,(H,24,25)(H,26,30)/b17-10+/t22-,23-/m0/s1
SMILES Code
CC(C=C)([C@@]12C=C(O)C(N3[C@@]1(N(OC)C4=CC=CC=C24)NC(/C3=C\C5=CN=CN5)=O)=O)C
Purity
>98% (or refer to the Certificate of Analysis)
Shipping Condition
Shipped under ambient temperature as non-hazardous chemical. This product is stable enough for a few weeks during ordinary shipping and time spent in Customs.
Storage Condition
Dry, dark and at 0 - 4 C for short term (days to weeks) or -20 C for long term (months to years).
Solubility
Soluble in DMSO, not in water
Shelf Life
>2 years if stored properly
Drug Formulation
This drug may be formulated in DMSO
Stock Solution Storage
0 - 4 C for short term (days to weeks), or -20 C for long term (months).
HS Tariff Code
2934.99.9001
Biological target:
Meleagrin is a class of FabI inhibitor.
In vitro activity:
The isolated FabI inhibitor was determined to be meleagrin by mass spectroscopy and nuclear magnetic resonance spectral analyses, and its more active and inactive derivatives were chemically prepared. Consistent with their selective inhibition of Staphylococcus aureus FabI, meleagrin and its more active derivatives directly bound to S. aureus FabI in a fluorescence quenching assay, inhibited intracellular fatty acid biosynthesis and growth of S. aureus, and increased the minimum inhibitory concentration for fabI-overexpressing S. aureus.
Reference: PLoS One. 2013 Nov 28;8(11):e78922. https://pubmed.ncbi.nlm.nih.gov/24312171/
In vivo activity:
Lung fibrosis was induced in mice by a single intratracheal instillation of 2.5 mg/kg bleomycin. Mice were given 5 mg/kg meleagrin daily either for 3 weeks after bleomycin administration in the treatment group or 2 weeks before and 3 weeks after bleomycin administration in the protection group. Meleagrin was noted to restore the oxidant-antioxidant balance, as evidenced by lower MDA contents and higher levels of SOD and catalase activities and GSH content compared to the bleomycin group. Meleagrin also activated the Nrf2/HO-1 antioxidant signaling pathway and inhibited TLR4 and NF-κB gene expression, with a subsequent decreased release of pro-inflammatory cytokines (TNF-α, IL-6 and IFN-γ). Additionally, meleagrin inhibited bleomycin-induced apoptosis by abating the activities of pro-apoptotic proteins Bax and caspase-3 while elevating Bcl2.
Reference: Biomedicines. 2022 May 18;10(5):1164. https://pubmed.ncbi.nlm.nih.gov/35625905/
Preparing Stock Solutions
The following data is based on the
product
molecular weight
433.47
Batch specific molecular weights may vary
from batch to batch
due to the degree of hydration, which will
affect the solvent
volumes required to prepare stock solutions.
| Concentration / Solvent Volume / Mass |
1 mg |
5 mg |
10 mg |
| 1 mM |
1.15 mL |
5.76 mL |
11.51 mL |
| 5 mM |
0.23 mL |
1.15 mL |
2.3 mL |
| 10 mM |
0.12 mL |
0.58 mL |
1.15 mL |
| 50 mM |
0.02 mL |
0.12 mL |
0.23 mL |
Formulation protocol:
1. Mady MS, Mohyeldin MM, Ebrahim HY, Elsayed HE, Houssen WE, Haggag EG, Soliman RF, El Sayed KA. The indole alkaloid meleagrin, from the olive tree endophytic fungus Penicillium chrysogenum, as a novel lead for the control of c-Met-dependent breast cancer proliferation, migration and invasion. Bioorg Med Chem. 2016 Jan 15;24(2):113-22. doi: 10.1016/j.bmc.2015.11.038. Epub 2015 Nov 28. PMID: 26692349; PMCID: PMC4703546.
2. Zheng CJ, Sohn MJ, Lee S, Kim WG. Meleagrin, a new FabI inhibitor from Penicillium chryosogenum with at least one additional mode of action. PLoS One. 2013 Nov 28;8(11):e78922. doi: 10.1371/journal.pone.0078922. PMID: 24312171; PMCID: PMC3842914.
3. Elhady SS, Goda MS, Mehanna ET, Elfaky MA, Koshak AE, Noor AO, Bogari HA, Malatani RT, Abdelhameed RFA, Wahba AS. Meleagrin Isolated from the Red Sea Fungus Penicillium chrysogenum Protects against Bleomycin-Induced Pulmonary Fibrosis in Mice. Biomedicines. 2022 May 18;10(5):1164. doi: 10.3390/biomedicines10051164. PMID: 35625905; PMCID: PMC9138525.
In vitro protocol:
1. Mady MS, Mohyeldin MM, Ebrahim HY, Elsayed HE, Houssen WE, Haggag EG, Soliman RF, El Sayed KA. The indole alkaloid meleagrin, from the olive tree endophytic fungus Penicillium chrysogenum, as a novel lead for the control of c-Met-dependent breast cancer proliferation, migration and invasion. Bioorg Med Chem. 2016 Jan 15;24(2):113-22. doi: 10.1016/j.bmc.2015.11.038. Epub 2015 Nov 28. PMID: 26692349; PMCID: PMC4703546.
2. Zheng CJ, Sohn MJ, Lee S, Kim WG. Meleagrin, a new FabI inhibitor from Penicillium chryosogenum with at least one additional mode of action. PLoS One. 2013 Nov 28;8(11):e78922. doi: 10.1371/journal.pone.0078922. PMID: 24312171; PMCID: PMC3842914.
In vivo protocol:
1. Elhady SS, Goda MS, Mehanna ET, Elfaky MA, Koshak AE, Noor AO, Bogari HA, Malatani RT, Abdelhameed RFA, Wahba AS. Meleagrin Isolated from the Red Sea Fungus Penicillium chrysogenum Protects against Bleomycin-Induced Pulmonary Fibrosis in Mice. Biomedicines. 2022 May 18;10(5):1164. doi: 10.3390/biomedicines10051164. PMID: 35625905; PMCID: PMC9138525.
2. Mady MS, Mohyeldin MM, Ebrahim HY, Elsayed HE, Houssen WE, Haggag EG, Soliman RF, El Sayed KA. The indole alkaloid meleagrin, from the olive tree endophytic fungus Penicillium chrysogenum, as a novel lead for the control of c-Met-dependent breast cancer proliferation, migration and invasion. Bioorg Med Chem. 2016 Jan 15;24(2):113-22. doi: 10.1016/j.bmc.2015.11.038. Epub 2015 Nov 28. PMID: 26692349; PMCID: PMC4703546.
1: Zheng CJ, Sohn MJ, Lee S, Kim WG. Meleagrin, a new FabI inhibitor from Penicillium chryosogenum with at least one additional mode of action. PLoS One. 2013 Nov 28;8(11):e78922. doi: 10.1371/journal.pone.0078922. eCollection 2013. PubMed PMID: 24312171; PubMed Central PMCID: PMC3842914.
2: Ries MI, Ali H, Lankhorst PP, Hankemeier T, Bovenberg RA, Driessen AJ, Vreeken RJ. Novel key metabolites reveal further branching of the roquefortine/meleagrin biosynthetic pathway. J Biol Chem. 2013 Dec 27;288(52):37289-95. doi: 10.1074/jbc.M113.512665. Epub 2013 Nov 13. PubMed PMID: 24225953; PubMed Central PMCID: PMC3873581.
3: Qin Y, Bao L, Gao M, Chen M, Lei Y, Liu G, Qu Y. Penicillium decumbens BrlA extensively regulates secondary metabolism and functionally associates with the expression of cellulase genes. Appl Microbiol Biotechnol. 2013 Dec;97(24):10453-67. doi: 10.1007/s00253-013-5273-3. Epub 2013 Oct 10. PubMed PMID: 24113825.
4: Ali H, Ries MI, Nijland JG, Lankhorst PP, Hankemeier T, Bovenberg RA, Vreeken RJ, Driessen AJ. A branched biosynthetic pathway is involved in production of roquefortine and related compounds in Penicillium chrysogenum. PLoS One. 2013 Jun 12;8(6):e65328. doi: 10.1371/journal.pone.0065328. Print 2013. PubMed PMID: 23776469; PubMed Central PMCID: PMC3680398.
5: Han Z, Sun J, Zhang Y, He F, Xu Y, Matsumura K, He LS, Qiu JW, Qi SH, Qian PY. iTRAQ-based proteomic profiling of the barnacle Balanus amphitrite in response to the antifouling compound meleagrin. J Proteome Res. 2013 May 3;12(5):2090-100. doi: 10.1021/pr301083e. Epub 2013 Apr 24. PubMed PMID: 23540395.
6: Kim HY, Park HM, Lee CH. Mass spectrometry-based chemotaxonomic classification of Penicillium species (P. echinulatum, P. expansum, P. solitum, and P. oxalicum) and its correlation with antioxidant activity. J Microbiol Methods. 2012 Sep;90(3):327-35. doi: 10.1016/j.mimet.2012.06.006. Epub 2012 Jun 23. PubMed PMID: 22732319.
7: GarcÃa-Estrada C, Ullán RV, Albillos SM, Fernández-Bodega MÃ
