Cladosporin
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| Category | Antibiotics |
| Catalog number | BBF-00647 |
| CAS | 35818-31-6 |
| Molecular Weight | 292.33 |
| Molecular Formula | C16H20O5 |
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Description
It is produced by the strain of Cladosporium cladosporiodes. Cladosporin has the activity of weak resistance to gram-positive bacteria, tinea trichoderma, microspora, potato filaria and other fungi.
Specification
| Synonyms | 3,4-dihydro-6,8-dihydroxy-3-(6-methyltetrahydropyran-2-ylmethyl)isocoumarin; asperentin; cladosporin; isocladosporin |
| IUPAC Name | (3R)-6,8-dihydroxy-3-[[(2R,6S)-6-methyloxan-2-yl]methyl]-3,4-dihydroisochromen-1-one |
| Canonical SMILES | CC1CCCC(O1)CC2CC3=C(C(=CC(=C3)O)O)C(=O)O2 |
| InChI | InChI=1S/C16H20O5/c1-9-3-2-4-12(20-9)8-13-6-10-5-11(17)7-14(18)15(10)16(19)21-13/h5,7,9,12-13,17-18H,2-4,6,8H2,1H3/t9-,12+,13+/m0/s1 |
| InChI Key | WOMKDMUZNBFXKG-ZWKOPEQDSA-N |
Properties
| Appearance | Colorless Acicular Crystalline |
| Antibiotic Activity Spectrum | fungi |
| Boiling Point | 543.4±45.0 °C | Condition: Press: 760 Torr |
| Melting Point | 188.5-189 °C |
| Density | 1.261±0.06 g/cm3 |
| Solubility | Soluble in ethanol, ethyl acetate, chloroform |
Reference Reading
1. Specific Stereoisomeric Conformations Determine the Drug Potency of Cladosporin Scaffold against Malarial Parasite
D Srinivasa Reddy, Rajesh G Gonnade, Amit Sharma, Palak Babbar, Nipun Malhotra, Goraknath R Jachak, Manmohan Sharma, Karl Harlos, Manickam Yogavel, Pronay Das, Dhanasekaran Shanmugam J Med Chem . 2018 Jul 12;61(13):5664-5678. doi: 10.1021/acs.jmedchem.8b00565.
The dependence of drug potency on diastereomeric configurations is a key facet. Using a novel general divergent synthetic route for a three-chiral center antimalarial natural product cladosporin, we built its complete library of stereoisomers (cladologs) and assessed their inhibitory potential using parasite-, enzyme-, and structure-based assays. We show that potency is manifest via tetrahyropyran ring conformations that are housed in the ribose binding pocket of parasite lysyl tRNA synthetase (KRS). Strikingly, drug potency between top and worst enantiomers varied 500-fold, and structures of KRS-cladolog complexes reveal that alterations at C3 and C10 are detrimental to drug potency whereas changes at C3 are sensed by rotameric flipping of glutamate 332. Given that scores of antimalarial and anti-infective drugs contain chiral centers, this work provides a new foundation for focusing on inhibitor stereochemistry as a facet of antimicrobial drug development.
2. Design and Synthesis of Metabolically Stable tRNA Synthetase Inhibitors Derived from Cladosporin
Thomas Aust, Arnaud Thevenon, Dominic Hoepfner, Esther Schmitt, Patrick Rollin, Carsten Spanka, Maude Patoor, Madeleine Livendahl, Laure C Bouchez, Beatrice Ranieri, Christian Studer, Marion Rusch, Karl Gademann Chembiochem . 2019 Mar 1;20(5):644-649. doi: 10.1002/cbic.201800587.
Selective and specific inhibitors of Plasmodium falciparum lysyl-tRNA synthetase represent promising therapeutic antimalarial avenues. Cladosporin was identified as a potent P. falciparum lysyl-tRNA synthetase inhibitor, with an activity against parasite lysyl-tRNA synthetase >100-fold more potent than that of the activity registered against the human enzyme. Despite its compelling activity, cladosporin exhibits poor oral bioavailability; a critical requirement for antimalarial drugs. Thus, the quest to develop metabolically stable cladosporin-derived analogues, while retaining similar selectivity and potency to that of the natural compound, has begun. Chemogenomic profiling of a designed library allowed an entirely innovative structure-activity relationship study to be initiated; this shed light on structural evidence of a privileged scaffold with a unique activity against tRNA synthetases.
3. Inhibition of Plasmodium falciparum Lysyl-tRNA Synthetase via a Piperidine-Ring Scaffold Inspired Cladosporin Analogues
Amit Sharma, Palak Babbar, Siddhartha Mishra, Swati Gupta, Suhel Parvez, Yogavel Manickam, Haruhisa Kikuchi, Mizuki Sato, Karl Harlos Chembiochem . 2021 Jul 15;22(14):2468-2477. doi: 10.1002/cbic.202100212.
Plasmodium falciparum lysyl-tRNA synthetase (PfKRS) represents a promising therapeutic anti-malarial target. Cladosporin was identified as a selective and potent PfKRS inhibitor but lacks metabolic stability. Here, we report chemical synthesis, biological evaluation and structural characterization of analogues where the tetrahydropyran (THP) frame of cladosporin is replaced with the piperidine ring bearing functional group variations. Thermal binding, enzymatic, kinetic and parasitic assays complemented with X-ray crystallography reveal compounds that are moderate in potency. Co-crystals of Cla-B and Cla-C with PfKRS reveal key atomic configurations that allow drug binding to and inhibition of the enzyme. Collectively these piperidine ring scaffold inhibitors lay a framework for further structural editing and functional modifications of the cladosporin scaffold to obtain a potent lead.
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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 ╳
