Ilamycin A
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| Category | Antibiotics |
| Catalog number | BBF-01494 |
| CAS | 11006-41-0 |
| Molecular Weight | 1042.22 |
| Molecular Formula | C54H75N9O12 |
| Purity | >97% |
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Description
Ilamycin A is produced by the strain of Str. islandicus A-165-Z1. It is resistant to mycobacteria, including human mycobacterium tuberculosis, and also to streptomycin resistant bacteria.
Specification
| IUPAC Name | (2S,5S,8S,11S,14S,17S,20S,22S)-5-[(E)-but-2-enyl]-23-hydroxy-14-[(4-hydroxy-3-nitrophenyl)methyl]-10,17,19,22-tetramethyl-2,11-bis(2-methylpropyl)-8-[[1-[2-(oxiran-2-yl)propan-2-yl]indol-3-yl]methyl]-1,4,7,10,13,16,19-heptazabicyclo[18.3.1]tetracosane-3,6,9,12,15,18,24-heptone |
| Canonical SMILES | CC=CCC1C(=O)NC(C(=O)N(C(C(=O)NC(C(=O)NC(C(=O)N(C2CC(C(N(C2=O)C(C(=O)N1)CC(C)C)O)C)C)C)CC3=CC(=C(C=C3)O)[N+](=O)[O-])CC(C)C)C)CC4=CN(C5=CC=CC=C54)C(C)(C)C6CO6 |
| InChI | InChI=1S/C54H75N9O12/c1-12-13-17-36-46(65)58-38(26-34-27-61(54(8,9)45-28-75-45)39-18-15-14-16-35(34)39)52(71)59(10)41(21-29(2)3)48(67)57-37(24-33-19-20-44(64)40(25-33)63(73)74)47(66)55-32(7)51(70)60(11)43-23-31(6)50(69)62(53(43)72)42(22-30(4)5)49(68)56-36/h12-16,18-20,25,27,29-32,36-38,41-43,45,50,64,69H,17,21-24,26,28H2,1-11H3,(H,55,66)(H,56,68)(H,57,67)(H,58,65)/b13-12+/t31-,32-,36-,37-,38-,41-,42-,43-,45?,50?/m0/s1 |
| InChI Key | JSZUQPCUWLSQDN-JJRQYJSGSA-N |
Properties
| Appearance | Yellow Powder |
| Antibiotic Activity Spectrum | mycobacteria |
| Melting Point | 163-169°C |
Reference Reading
1. Total Synthesis and Biological Evaluation of Modified Ilamycin Derivatives
Jennifer Greve, Axel Mogk, Uli Kazmaier Mar Drugs. 2022 Oct 3;20(10):632. doi: 10.3390/md20100632.
Ilamycins/rufomycins are marine cycloheptapeptides containing unusual amino acids. Produced by Streptomyces sp., these compounds show potent activity against a range of mycobacteria, including multidrug-resistant strains of Mycobacterium tuberculosis. The cyclic peptides target the AAA+ protein ClpC1 that, together with the peptidases ClpP1/ClpP2, forms an essential ATP-driven protease. Derivatives of the ilamycins with a simplified tryptophane unit are synthesized in a straightforward manner. The ilamycin derivative 26 with a cyclic hemiaminal structure is active in the nM-range against several mycobacterial strains and shows no significant cytotoxicity. In contrast, derivative 27, with a glutamic acid at this position, is significantly less active, with MICs in the mid µM-range. Detailed investigations of the mode of action of 26 indicate that 26 deregulates ClpC1 activity and strongly enhances ClpC1-WT ATPase activity. The consequences of 26 on ClpC1 proteolytic activities were substrate-specific, suggesting dual effects of 26 on ClpC1-WT function. The positive effect relates to ClpC1-WT ATPase activation, and the negative to competition with substrates for binding to the ClpC1 NTD.
2. Medium optimization and subsequent fermentative regulation enabled the scaled-up production of anti-tuberculosis drug leads ilamycin-E1/E2
Zhiying Fan, Nian Tong, Zhoukang Zhuang, Cheng Ma, Junying Ma, Jianhua Ju, Yanwen Duan, Xiangcheng Zhu Biotechnol J. 2022 Apr;17(4):e2100427. doi: 10.1002/biot.202100427. Epub 2022 Feb 10.
Background: Tuberculosis (TB) and its evolving drug resistance have exerted severe threats on the global health, hence it is still essential to develop novel anti-TB antibiotics. Ilamycin-E1/E2 is a pair of cycloheptapeptide enantiomers obtained from a marine Streptomyces atratus SCSIO ZH16-ΔilaR mutant, and has presented significant anti-TB activities as promising drug lead compounds, but their clinical development has been hampered by low fermentation titers. Main methods and major results: By applying the statistical Plackett-Burman design (PBD) model, bacterial peptone was first screened out as the only significant but negative factor to affect the ilamycin-E1/E2 production. Subsequent single factor optimization in shaking flasks revealed that the replacement of bacterial peptone with malt extract could not only eliminate the accumulation of porphyrin-type competitive byproducts but also improve the titer of ilamycin-E1/E2 from original 13.6 ± 0.8 to 142.7 ± 5.7 mg L-1 , about 10.5-fold increase. Next, a pH coordinated feeding strategy was adopted in 30 L fermentor and obtained 169.8 ± 2.5 mg L-1 ilamycin-E1/E2, but further scaled-up production in 300 L fermentor only gave a titer of 131.5 ± 7.5 mg L-1 due to the unsynchronization of feeding response and pH change. Consequently, a continuous pulse feeding strategy was utilized in 300 L fermentor to solve the above problem and finally achieved 415.7 ± 29.2 mg L-1 ilamycin-E1/E2, representing a 30.5-fold improvement. Implication: Our work has provided a solid basis to acquire sufficient ilamycin-E1/E2 lead compounds and then support their potential anti-TB drug development.
3. Semi-Synthesis of Marine-Derived Ilamycin F Derivatives and Their Antitubercular Activities
Jun Li, Zhiyong Liu, Mingye Hong, Changli Sun, Tianyu Zhang, Hua Zhang, Jianhua Ju, Junying Ma Front Chem. 2021 Oct 29;9:774555. doi: 10.3389/fchem.2021.774555. eCollection 2021.
Tuberculosis (TB) is still a global disease threatening people's lives. With the emergence of multi-drug-resistant Mycobacterium tuberculosis the prevention and control of tuberculosis faces new challenges, and the burden of tuberculosis treatment is increasing among the world. Ilamycins are novel cyclopeptides with potent anti-TB activities, which have a unique target protein against M. tuberculosis and drug-resistant strains. Herein, ilamycin F, a major secondary metabolite isolated from the marine-derived mutant strain Streptomyces atratus SCSIO ZH16 ΔilaR, is used as a scaffold to semi-synthesize eighteen new ilamycin derivatives (ilamycin NJL1-NJL18, 1-18). Our study reveals that four of ilamycin NJLs (1, 6, 8, and 10) have slightly stronger anti-TB activities against Mtb H37Rv (minimum inhibitory concentration, 1.6-1.7 μM) compared with that of ilamycin F on day 14th, but obviously display more potent activities than ilamycin F on day 3rd, indicating anti-TB activities of these derivatives with fast-onset effect. In addition, cytotoxic assays show most ilamycin NJLs with low cytotoxicity except ilamycin NJL1 (1). These findings will promote the further exploration of structure-activity relationships for ilamycins and the development of anti-TB drugs.
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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 ╳
