Rakicidin A
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| Category | Antibiotics |
| Catalog number | BBF-02173 |
| CAS | |
| Molecular Weight | 606.79 |
| Molecular Formula | C32H54N4O7 |
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Description
Rakicidin A is originally isolated from Micromonospora sp. R385-2. It has anti-tumor activity in vitro with the IC50 of 40 μg/mL.
Specification
| IUPAC Name | 2-[(9Z)-7,14-dimethyl-11-methylidene-15-(14-methylpentadecan-2-yl)-2,5,8,13-tetraoxo-1-oxa-4,7,12-triazacyclopentadec-9-en-3-yl]-2-hydroxyacetamide |
| Canonical SMILES | CC1C(OC(=O)C(NC(=O)CN(C(=O)C=CC(=C)NC1=O)C)C(C(=O)N)O)C(C)CCCCCCCCCCCC(C)C |
| InChI | InChI=1S/C32H54N4O7/c1-21(2)16-14-12-10-8-7-9-11-13-15-17-22(3)29-24(5)31(41)34-23(4)18-19-26(38)36(6)20-25(37)35-27(32(42)43-29)28(39)30(33)40/h18-19,21-22,24,27-29,39H,4,7-17,20H2,1-3,5-6H3,(H2,33,40)(H,34,41)(H,35,37)/b19-18- |
| InChI Key | NODOLTRBPIFGCQ-HNENSFHCSA-N |
Properties
| Appearance | Colorless Amorphous Solid |
| Antibiotic Activity Spectrum | neoplastics (Tumor) |
Reference Reading
1. Two new rakicidin derivatives from marine Micromonospora chalcea FIM-R160609
Li Chen, Lijun Xie, Wei Zhao, Jian Zhou, Honglei Jiang, Wei Liu, Hong Jiang, Feng Lin Nat Prod Res. 2022 Nov 9;1-8. doi: 10.1080/14786419.2022.2144297. Online ahead of print.
The establishment of structure activity relationship (SAR) for rakicidin derivatives is pretty vital to develop rakicidins as a new type of anti-cancer agents. Herein, two novel rakicidin derivatives, compounds B1-1 (1) and B1-2 (2), a cyclic depsipeptide and a chain lipopeptide, respectively, were isolated from culture broth of Micromonospora chalcea FIM-R160609, and their structures were elucidated clearly by extensive NMR and HR-ESI-MS analyses. Following, their cytotoxic activities were evaluated against HCT-8 and PANC-1 human cancer cell lines under hypoxic and normoxic conditions. Their activities were significantly decreased when compared with that of rakicidin B1. These results demonstrated that the double bond located on the position 9 and 10 of conjugated diene unit and cycle-type structure plays an important role in keeping the biological activity of rakicidins. Furthermore, the positive effect of double bond and cycle form on the anti-bacterial activities were also confirmed by testing their inhibitory activities against gram positive bacteria. This work will definitely diversify the SAR of rakicidins and provide the guidance for the design of new potent rakicidin analogues.
2. Syntheses and anti-pancreatic cancer activities of rakicidin A analogues
Jian Chen, Jingpei Li, Lingling Wu, Yan Geng, Jianming Yu, Chuanke Chong, Mengmeng Wang, Yuan Gao, Cuigai Bai, Yahui Ding, Yue Chen, Quan Zhang Eur J Med Chem. 2018 May 10;151:601-627. doi: 10.1016/j.ejmech.2018.03.078. Epub 2018 Mar 29.
Pancreatic ductal adenocarcinoma (PDAC) is a highly aggressive malignant tumor and resistant to most therapies. Pancreatic cancer stem cells (PCSCs) had critical role in regulating PDAC progression, metastasis, and drug resistance. Therefore, targeting PCSCs is considered to be a promising strategy for treatment of PDAC. However, there is no effective drug that can selectively ablate PCSCs. A series of twenty rakicidin A analogues were synthesized via a combinatorial strategy and evaluated for their anti-PDAC activities, and the structure-activity relationship was also discussed. Compound 32g was prepared in 14 linear steps with 5.05% overall yield, which is much more efficient than our previously reported total synthesis of rakicidin A (19 linear steps with 0.19% yield). In a highly metastatic pancreatic cancer cell line ASPC-1, compound 32g showed about 4 times higher potency (IC50 = 0.022 μM) than rakicidin A (IC50 = 0.082 μM) at hypoxia condition, and 12 folds of hypoxia selectivity (IC50 = 0.27 μM at nomoxia condition). In contrast, the activity of adriamycin in the same hypoxic condition decreased. The percentage of PCSCs (with CD24+CD44+ESA+ biomarker), activity of ALDH, and the number of tumorspheres in PANC-1 cells were greatly reduced after treatment of 32g. More importantly, the tumor-initiating frequency was reduced by 19 folds after the treatment of 32g, which is better than that of rakicidin A (reduction of 4.7 folds).
3. Application of Lithiation-Borylation to the Total Synthesis of (-)-Rakicidin F
Christian P Bold, Kay Yeung, Felix Pape, Daniel Kaiser, Varinder K Aggarwal Org Lett. 2022 Dec 30;24(51):9398-9402. doi: 10.1021/acs.orglett.2c03716. Epub 2022 Dec 20.
The stereochemistry of the lipophilic side chain of (+)-rakicidin F had not been determined until recently. Using our lithiation-borylation methodology ("assembly line synthesis") we were able to efficiently prepare the all-syn isomer as well as the C-21 epimer of the side chain, and comparison with the natural product suggested that the natural product had all-syn stereochemistry. Completion of the total synthesis using a macrolactamization of the northern amide enabled us to confirm Wang and Chen's stereochemical findings for the structure of (+)-rakicidin F.
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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 ╳
