Kendomycin
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| Category | Enzyme inhibitors |
| Catalog number | BBF-03799 |
| CAS | 183202-73-5 |
| Molecular Weight | 486.64 |
| Molecular Formula | C29H42O6 |
| Purity | >95% by HPLC |
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Description
Kendomycin is an endothelin receptor antagonist and proteasome inhibitor. It induces apoptosis in lymphoma. It is a potent antibacterial agent against gram-positive and gram-negative bacteria, including MRSA strains.
Specification
| Synonyms | TAN 2162 |
| Storage | Store at -20°C |
| IUPAC Name | (1R,9S,10S,12S,14E,16S,19R,20R,21S,22R)-3,9,21-trihydroxy-5,10,12,14,16,20,22-heptamethyl-23,24-dioxatetracyclo[17.3.1.16,9.02,7]tetracosa-2,5,7,14-tetraen-4-one |
| Canonical SMILES | CC1CCC2C(C(C(C(O2)C3=C(C(=O)C(=C4C3=CC(O4)(C(CC(CC(=C1)C)C)C)O)C)O)C)O)C |
| InChI | InChI=1S/C29H42O6/c1-14-8-9-22-18(5)24(30)19(6)28(34-22)23-21-13-29(33,17(4)12-16(3)11-15(2)10-14)35-27(21)20(7)25(31)26(23)32/h10,13-14,16-19,22,24,28,30,32-33H,8-9,11-12H2,1-7H3/b15-10+/t14-,16+,17-,18-,19+,22+,24-,28+,29+/m0/s1 |
| InChI Key | HKLDUJXJTQJSEJ-OLXNOMCWSA-N |
| Source | Streptomyces sp. |
Properties
| Appearance | Yellow Solid |
| Antibiotic Activity Spectrum | Gram-positive bacteria; Gram-negative bacteria |
| Boiling Point | 678.5±55.0°C at 760 mmHg |
| Density | 1.43 g/cm3 |
| Solubility | Soluble in ethanol, methanol, DMF, DMSO |
Reference Reading
1. Investigations to the Antibacterial Mechanism of Action of Kendomycin
Mathias Herrmann, Markus Bischoff, Indranil Chatterjee, Rolf Müller, Manfred Rohde, Yasser A Elnakady, Michaele Josten, Hans-Georg Sahl PLoS One . 2016 Jan 21;11(1):e0146165. doi: 10.1371/journal.pone.0146165.
Purpose:The emergence of bacteria that are resistant to many currently used drugs emphasizes the need to discover and develop new antibiotics that are effective against such multi-resistant strains. Kendomycin is a novel polyketide that has a unique quinone methide ansa structure and various biological properties. This compound exhibits strong antibacterial activity against Gram-negative and Gram-positive bacteria, including methicillin-resistant Staphylococcus aureus (MRSA). Despite the promise of kendomycinin in several therapeutic areas, its mode of action has yet to be identified.Methods:In this study, we used a multidisciplinary approach to gain insight into the antibacterial mechanism of this compound.Results:The antibacterial activity of kendomycin appears to be bacteriostatic rather than bactericidal. Kendomycin inhibited the growth of the MRSA strain COL at a low concentration (MIC of 5 μg/mL). Proteomic analysis and gene transcription profiling of kendomycin-treated cells indicated that this compound affected the regulation of numerous proteins and genes involved in central metabolic pathways, such as the tricarboxylic acid (TCA) cycle (SdhA) and gluconeogenesis (PckA and GapB), cell wall biosynthesis and cell division (FtsA, FtsZ, and MurAA), capsule production (Cap5A and Cap5C), bacterial programmed cell death (LrgA and CidA), the cellular stress response (ClpB, ClpC, ClpP, GroEL, DnaK, and GrpE), and oxidative stress (AhpC and KatA). Electron microscopy revealed that kendomycin strongly affected septum formation during cell division. Most kendomycin-treated cells displayed incomplete septa with abnormal morphology.Conclusions:Kendomycin might directly or indirectly affect the cell division machinery, protein stability, and programmed cell death in S. aureus. Additional studies are still needed to obtain deeper insight into the mode of action of kendomycin.
2. Identification and Heterologous Expression of the Kendomycin B Biosynthetic Gene Cluster from Verrucosispora sp. SCSIO 07399
Jianhua Ju, Yucheng Gu, Jiang Chen, Shanwen Zhang, Xinpeng Tian, Yingying Chen Mar Drugs . 2021 Nov 26;19(12):673. doi: 10.3390/md19120673.
Verrucosisporasp. SCSIO 07399, a rare marine-derived actinomycete, produces a set of ansamycin-like polyketides kendomycin B-D (1-3) which possess potent antibacterial activities and moderate tumor cytotoxicity. Structurally, kendomycin B-D contain a unique aliphatic macrocyclicansascaffold in which the highly substituted pyran ring is connected to the quinone moiety. In this work, a type I/type III polyketide synthase (PKS) hybrid biosynthetic gene cluster coding for assembly of kendomycin B (kmy), and covering 33 open reading frames, was identified fromVerrucosisporasp. SCSIO 07399. Thekmycluster was found to be essential for kendomycin B biosynthesis as verified by gene disruption and heterologous expression. Correspondingly, a biosynthetic pathway was proposed based on bioinformatics, cluster alignments, and previous research. Additionally, the role of type III PKS for generating the precursor unit 3,5-dihydroxybenzoic acid (3,5-DHBA) was demonstrated by chemical complementation, and type I PKS executed the polyketide chain elongation. Thekmycluster was found to contain a positive regulatory genekmy4whose regulatory effect was identified using real-time quantitative PCR (RT-qPCR). These advances shed important new insights into kendomycin B biosynthesis and help to set the foundation for further research aimed at understanding and exploiting the carbacylicansascaffold.
3. Interactions of the natural product kendomycin and the 20S proteasome
Yasser Elnakady, Michael Groll, Anna-Lena Späth, Wolfgang Heinemeyer, Philipp Beck, Rolf Müller J Mol Biol . 2014 Sep 9;426(18):3108-3117. doi: 10.1016/j.jmb.2014.06.019.
Natural products are a valuable source for novel lead structures in drug discovery, but for the majority of isolated bioactive compounds, the cellular targets are unknown. The structurally unique ansa-polyketide kendomycin (KM) was reported to exert its potent cytotoxic effects via impairment of the ubiquitin proteasome system, but the exact mode of action remained unclear. Here, we present a systematic biochemical characterization of KM-proteasome interactions in vitro and in vivo, including complex structures of wild type and mutant yeast 20S proteasome with KM. Our results provide evidence for a polypharmacological mode of action for KM's cytotoxic effect on cancer cells.
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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 ╳
