Cladosporin
(Synonyms: 枝孢菌素) 目录号 : GC65557
Cladosporin 是一种真菌代谢物，在 Cladosporium cladosporioid 的菌丝体中产生。含浓度 75 μg/mL Cladosporin 的琼脂培养基可完全抑制多种皮肤癣菌的生长。
Cas No.:35818-31-6
Sample solution is provided at 25 µL, 10mM.
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Quality Control & SDS
- View current batch:
- Purity: >98.00%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
Cladosporin is a fungal metabolite produced in good yield in the mycelium of Cladosporium cladosporioid. Cladosporin completely inhibits growth of severa dermatophytes on agar medium at a concentration of 75 μg/mL[1].
[1]. P M Scott, et al. Cladosporin, a new antifungal metabolite from Cladosporium cladosporioides. J Antibiot (Tokyo). 1971 Nov;24(11):747-55.
| Cas No. | 35818-31-6 | SDF | Download SDF |
| 别名 | 枝孢菌素 | ||
| 分子式 | C16H20O5 | 分子量 | 292.33 |
| 溶解度 | 储存条件 | Store at -20°C, stored under nitrogen | |
| General tips | 请根据产品在不同溶剂中的溶解度选择合适的溶剂配制储备液；一旦配成溶液，请分装保存，避免反复冻融造成的产品失效。 储备液的保存方式和期限：-80°C 储存时，请在 6 个月内使用，-20°C 储存时，请在 1 个月内使用。 为了提高溶解度，请将管子加热至37℃，然后在超声波浴中震荡一段时间。 |
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| Shipping Condition | 评估样品解决方案：配备蓝冰进行发货。所有其他可用尺寸：配备RT，或根据请求配备蓝冰。 | ||
| 制备储备液 | |||
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1 mg | 5 mg | 10 mg |
| 1 mM | 3.4208 mL | 17.104 mL | 34.2079 mL |
| 5 mM | 0.6842 mL | 3.4208 mL | 6.8416 mL |
| 10 mM | 0.3421 mL | 1.7104 mL | 3.4208 mL |
| 第一步：请输入基本实验信息（考虑到实验过程中的损耗，建议多配一只动物的药量） | ||||||||||
| 给药剂量 | mg/kg |  |
动物平均体重 | g | |
每只动物给药体积 | ul | |
动物数量 | 只 |
| 第二步：请输入动物体内配方组成（配方适用于不溶于水的药物；不同批次药物配方比例不同，请联系GLPBIO为您提供正确的澄清溶液配方） | ||||||||||
| % DMSO % % Tween 80 % saline | ||||||||||
| 计算重置 | ||||||||||
计算结果:
工作液浓度： mg/ml；
DMSO母液配制方法： mg 药物溶于 μL DMSO溶液（母液浓度 mg/mL，
体内配方配制方法：取 μL DMSO母液，加入 μL PEG300，混匀澄清后加入μL Tween 80，混匀澄清后加入 μL saline，混匀澄清。
1. 首先保证母液是澄清的；
2.
一定要按照顺序依次将溶剂加入，进行下一步操作之前必须保证上一步操作得到的是澄清的溶液，可采用涡旋、超声或水浴加热等物理方法助溶。
3. 以上所有助溶剂都可在 GlpBio 网站选购。
Chemical and Biological Study of Cladosporin, an Antimicrobial Inhibitor: A Review
Nat Prod Commun 2016 Oct;11(10):1595-1600.PMID:30549627doi
. Natural antifungal agents are generally broad-spectrum compounds with low mammalian and environmental toxicity. Cladosporin is a naturally occurring fungal metabolite mainly isolated from the endophytic fungus Cladosporium cladosporioides. This review article summarizes the chemistry and biological - properties of Cladosporin covering references published from 1971-2016, including the source, phytochemical characterization, biosynthesis, total synthesis, structure and activity (SAR), and biological activity of Cladosporin. Cladosporin exhibited potent antibacterial, antifungal, insecticidal, and anti-inflammatory activities, as well as plant growth regulatory effects. More importantly, Cladosporin was identified as having potent, nanomolar, antiparasitic activity against both Plasmodiumfalciparum blood and liver stages via specific inhibition of protein synthesis. This provides a new approach for the design of isocoumarin- based compounds for the treatment of malaria. Herbicidal activity and antifungal activity against Cryptococcus neoformans (C₅₀ value of 17.7 μg/mL) of Cladosporin are also described here in the review for the first time. Cladosporin selectively inhibited the growth of a monocot (agostis) and showed no activity against a dicot (lettuce), which indicates its great potential as a selective herbicide for monocots in agriculture use. The above data suggest that Cladosporin has great potential utility as a lead compound in the development of agrochemicals against certain plant pathogens and pharmaceuticals against drug-resistant bacteria and parasites.
Design, Synthesis, and Structural Analysis of Cladosporin-Based Inhibitors of Malaria Parasites
ACS Infect Dis 2021 Jun 11;7(6):1777-1794.PMID:33843204DOI:10.1021/acsinfecdis.1c00092.
Here we have described a systematic structure activity relationship (SAR) of a set of compounds inspired from Cladosporin, a tool compound that targets parasite (Plasmodium falciparum) lysyl tRNA synthetase (KRS). Four sets of analogues, synthesized based on point changes in the chemical scaffold of Cladosporin and other logical modifications and hybridizations, were assessed using high throughput enzymatic and parasitic assays along with in vitro pharmacokinetics. Co-crystallization of the most potent compound in our series (CL-2) with PfKRS revealed its structural basis of enzymatic binding and potency. Further, we report that CL-2 has performed better than Cladosporin in terms of metabolic stability. It thus represents a new lead for further optimization toward the development of antimalarial drugs. Collectively, along with a lead compound, the series offers insights on how even the slightest chemical modification might play an important role in enhancing or decreasing the potency of a chemical scaffold.
Cladosporin Derivatives Obtained by Biotransformation Provide Guidance for the Focused Derivatization of this Antimalarial Lead Compound
Chembiochem 2019 Mar 1;20(5):650-654.PMID:30347507DOI:10.1002/cbic.201800588.
Cladosporin, a natural product known for decades, has recently been discovered to display potent and selective antiplasmodial activity by inhibition of lysyl-tRNA synthetase. It was subjected to a panel of oxidative biotransformations with one fungal and two actinomycetes strains, as well as a triple mutant bacterial CYP102A1, yielding eight, mostly hydroxylated, derivatives. These new compounds covered a wide chemical space and contained two pairs of epimers in the tetrahydropyran ring. Although less potent than the parent compound, all analogues showed activity in a cell-based synthetase assay, thus demonstrating uptake and on-target activity in living cells with varying degrees of selectivity for the enzyme lysyl-tRNA synthetase from Plasmodium falciparum and highlighting sites suitable for synthesis of future Cladosporin analogues. Compounds with adjacent hydroxy functions showed different MS/MS fragmentation that can be explained in terms of an, in some cases, regioselective loss of water followed by a retro-Diels-Alder reaction.
Production of New Cladosporin Analogues by Reconstitution of the Polyketide Synthases Responsible for the Biosynthesis of this Antimalarial Agent
Angew Chem Int Ed Engl 2016 Jan 11;55(2):664-8.PMID:26783060DOI:10.1002/anie.201509345.
The antimalarial agent Cladosporin is a nanomolar inhibitor of the Plasmodium falciparum lysyl-tRNA synthetase, and exhibits activity against both blood- and liver-stage infection. Cladosporin can be isolated from the fungus Cladosporium cladosporioides, where it is biosynthesized by a highly reducing (HR) and a non-reducing (NR) iterative type I polyketide synthase (PKS) pair. Genome sequencing of the host organism and subsequent heterologous expression of these enzymes in Saccharomyces cerevisiae produced Cladosporin, confirming the identity of the putative gene cluster. Incorporation of a pentaketide intermediate analogue indicated a 5+3 assembly by the HR PKS Cla2 and the NR PKS Cla3 during Cladosporin biosynthesis. Advanced-intermediate analogues were synthesized and incorporated by Cla3 to furnish new Cladosporin analogues. A putative lysyl-tRNA synthetase resistance gene was identified in the Cladosporin gene cluster. Analysis of the active site emphasizes key structural features thought to be important in resistance to Cladosporin.
Inhibition of Plasmodium falciparum Lysyl-tRNA Synthetase via a Piperidine-Ring Scaffold Inspired Cladosporin Analogues
Chembiochem 2021 Jul 15;22(14):2468-2477.PMID:33969584DOI: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.