Nargenicin A1
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| Category | Antibiotics |
| Catalog number | BBF-04505 |
| CAS | 70695-02-2 |
| Molecular Weight | 515.60 |
| Molecular Formula | C28H37NO8 |
| Purity | ≥99% |
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Description
Nargenicin A1 is a macrolide antibiotic produced by Nocardia sp. that is effective against Gram-positive bacteria including taphylococcus and Clostridia. It shows more potent efficacy against methicilin resistant S. aureus (MRSA) than erythromycin and vancomycin.
Specification
| Synonyms | Antibiotic 47444; CP 47444; NSC 355066; Nodusmicin 9-(1H-pyrrole-2-carboxylate); 1H-Pyrrole-2-carboxylic acid,(1E,3R,4S,7S,8aS,10aR,11R,12R,13R,14R,14aS,14bS)-3,4,6,7,8,8a,10a,11,12,13,14,14a-dodecahydro-14-hydroxy-4-[(1R)-1-hydroxyethyl]-7-methoxy-1,3,13-trimethyl-6-oxo-11,14b-epoxy-14bH-naphth[2,1-e]oxecin-12-yl ester |
| Storage | Store at -20°C |
| IUPAC Name | [(1S,3R,4R,5R,6R,7S,8R,11S,13S,16S,17R,18E)-6-hydroxy-16-[(1R)-1-hydroxyethyl]-13-methoxy-5,17,19-trimethyl-14-oxo-2,15-dioxatetracyclo[9.8.0.01,7.03,8]nonadeca-9,18-dien-4-yl] 1H-pyrrole-2-carboxylate |
| Canonical SMILES | CC1C=C(C23C(CC(C(=O)OC1C(C)O)OC)C=CC4C2C(C(C(C4O3)OC(=O)C5=CC=CN5)C)O)C |
| InChI | InChI=1S/C28H37NO8/c1-13-11-14(2)28-17(12-20(34-5)27(33)35-23(13)16(4)30)8-9-18-21(28)22(31)15(3)24(25(18)37-28)36-26(32)19-7-6-10-29-19/h6-11,13,15-18,20-25,29-31H,12H2,1-5H3/b14-11+/t13-,15-,16-,17-,18-,20+,21+,22-,23+,24-,25-,28+/m1/s1 |
| InChI Key | YEUSSARNQQYBKH-SIMZXIQRSA-N |
Properties
| Appearance | Off-white Powder |
| Antibiotic Activity Spectrum | Gram-positive bacteria |
| Boiling Point | 718.3±60.0°C (Predicted) |
| Density | 1.31±0.1 g/cm3 (Predicted) |
| Solubility | Soluble in Methanol, DMSO |
Reference Reading
1. Novel Nargenicin A1 Analog Inhibits Angiogenesis by Downregulating the Endothelial VEGF/VEGFR2 Signaling and Tumoral HIF-1α/VEGF Pathway
Ye Seul Choi, Jang Mi Han, Hye Jin Jung, Dipesh Dhakal, Jae Kyung Sohng Biomedicines . 2020 Jul 29;8(8):252. doi: 10.3390/biomedicines8080252.
Targeting angiogenesis is an attractive strategy for the treatment of angiogenesis-related diseases, including cancer. We previously identified 23-demethyl 8,13-deoxynargenicin (compound9) as a novel nargenicin A1 analog with potential anticancer activity. In this study, we investigated the antiangiogenic activity and mode of action of compound9. This compound was found to effectively inhibit in vitro angiogenic characteristics, including the proliferation, invasion, capillary tube formation, and adhesion of human umbilical vein endothelial cells (HUVECs) stimulated by vascular endothelial growth factor (VEGF). Furthermore, compound9suppressed the neovascularization of the chorioallantoic membrane of growing chick embryos in vivo. Notably, the antiangiogenic properties of compound9were related to the downregulation of VEGF/VEGFR2-mediated downstream signaling pathways, as well as matrix metalloproteinase (MMP)-2 and MMP-9 expression in HUVECs. In addition, compound9was found to decrease the in vitro AGS gastric cancer cell-induced angiogenesis of HUVECs by blocking hypoxia-inducible factor-1α (HIF-1α) and VEGF expression in AGS cells. Collectively, our findings demonstrate for the first time that compound9is a promising antiangiogenic agent targeting both VEGF/VEGFR2 signaling in ECs and HIF-1α/VEGF pathway in tumor cells.
2. Identification of Cyclophilin A as a Potential Anticancer Target of Novel Nargenicin A1 Analog in AGS Gastric Cancer Cells
Woo-Haeng Lee, Hye Jin Jung, Jang Mi Han, Tae-Jin Oh, Jae Kyung Sohng Int J Mol Sci . 2021 Mar 1;22(5):2473. doi: 10.3390/ijms22052473.
We recently discovered a novel nargenicin A1 analog, 23-demethyl 8,13-deoxynargenicin (compound 9), with potential anti-cancer and anti-angiogenic activities against human gastric adenocarcinoma (AGS) cells. To identify the key molecular targets of compound 9, that are responsible for its biological activities, the changes in proteome expression in AGS cells following compound 9 treatment were analyzed using two-dimensional gel electrophoresis (2-DE), followed by MALDI/TOF/MS. Analyses using chemical proteomics and western blotting revealed that compound 9 treatment significantly suppressed the expression of cyclophilin A (CypA), a member of the immunophilin family. Furthermore, compound 9 downregulated CD147-mediated mitogen-activated protein kinase (MAPK) signaling pathway, including c-Jun N-terminal kinase (JNK) and extracellular signal-regulated protein kinase 1/2 (ERK1/2) by inhibiting the expression of CD147, the cellular receptor of CypA. Notably, the responses of AGS cells to CypA knockdown were significantly correlated with the anticancer and antiangiogenic effects of compound 9. CypA siRNAs reduced the expression of CD147 and phosphorylation of JNK and ERK1/2. In addition, the suppressive effects of CypA siRNAs on proliferation, migration, invasion, and angiogenesis induction of AGS cells were associated with G2/M cell cycle arrest, caspase-mediated apoptosis, inhibition of MMP-9 and MMP-2 expression, inactivation of PI3K/AKT/mTOR pathway, and inhibition of hypoxia-inducible factor-1α (HIF-1α) and vascular endothelial growth factor (VEGF) expression. The specific interaction between compound 9 and CypA was also confirmed using the drug affinity responsive target stability (DARTS) and cellular thermal shift assay (CETSA) approaches. Moreover, in silico docking analysis revealed that the structure of compound 9 was a good fit for the cyclosporin A binding cavity of CypA. Collectively, these findings provide a novel molecular basis for compound 9-mediated suppression of gastric cancer progression through the targeting of CypA.
3. Protective Effects of Nargenicin A1 against Tacrolimus-Induced Oxidative Stress in Hirame Natural Embryo Cells
Yung Hyun Choi, Hee-Jae Cha, Cheol Park, Gi-Young Kim, Min Ho Han, Da Hye Kwon, Su Jung Hwang, Su-Hyun Hong, Hyo-Jong Lee, Jin-Woo Jeong, Sang Hoon Hong, Heui-Soo Kim, Suhkmann Kim Int J Environ Res Public Health . 2019 Mar 22;16(6):1044. doi: 10.3390/ijerph16061044.
Tacrolimus is widely used as an immunosuppressant to reduce the risk of rejection after organ transplantation, but its cytotoxicity is problematic. Nargenicin A1 is an antibiotic extracted fromNocardia argentinensisand is known to have antioxidant activity, though its mode of action is unknown. The present study was undertaken to evaluate the protective effects of nargenicin A1 on DNA damage and apoptosis induced by tacrolimus in hirame natural embryo (HINAE) cells. We found that reduced HINAE cell survival by tacrolimus was due to the induction of DNA damage and apoptosis, both of which were prevented by co-treating nargenicin A1 or N-acetyl-l-cysteine, a reactive oxygen species (ROS) scavenger, with tacrolimus. In addition, apoptosis induction by tacrolimus was accompanied by increases in ROS generation and decreases in adenosine triphosphate (ATP) levels caused by mitochondrial dysfunction, and these changes were significantly attenuated in the presence of nargenicin A1, which further indicated tacrolimus-induced apoptosis involved an oxidative stress-associated mechanism. Furthermore, nargenicin A1 suppressed tacrolimus-induced B-cell lymphoma-2 (Bcl-2) down-regulation, Bax up-regulation, and caspase-3 activation. Collectively, these results demonstrate that nargenicin A1 protects HINAE cells against tacrolimus-induced DNA damage and apoptosis, at least in part, by scavenging ROS and thus suppressing the mitochondrial-dependent apoptotic pathway.
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Bio Calculators
* Our calculator is based on the following equation:
Concentration (start) x Volume (start) = Concentration (final) x Volume (final)
It is commonly abbreviated as: C1V1 = C2V2
* Total Molecular Weight:
g/mol
Tip: Chemical formula is case sensitive. C22H30N4O √ c22h30n40 ╳
