Macrosphelide L
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| Category | Enzyme inhibitors |
| Catalog number | BBF-02289 |
| CAS | |
| Molecular Weight | 342.34 |
| Molecular Formula | C16H22O8 |
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Description
It is produced by the strain of Periconia byssoides OUPS-N133. It is a cell adhesion inhibitor. It inhibits the adhesion of HL-60 cells to HU-VEC cells with IC50 of 5.6 μmol/L.
Specification
| IUPAC Name | (4R,7Z,9R,10S,16S)-9-hydroxy-4,10,16-trimethyl-1,5,11-trioxacyclohexadec-7-ene-2,6,12,15-tetrone |
| Canonical SMILES | CC1CC(=O)OC(C(=O)CCC(=O)OC(C(C=CC(=O)O1)O)C)C |
| InChI | InChI=1S/C16H22O8/c1-9-8-16(21)24-11(3)13(18)5-7-15(20)23-10(2)12(17)4-6-14(19)22-9/h4,6,9-12,17H,5,7-8H2,1-3H3/b6-4-/t9-,10+,11+,12-/m1/s1 |
| InChI Key | OJDUZZJLGZZTSF-RQKWENOMSA-N |
Properties
| Appearance | Colorless Oily Matter |
| Antibiotic Activity Spectrum | Neoplastics (Tumor) |
| Solubility | Soluble in Ethanol |
Reference Reading
1. Absolute stereostructures of cell adhesion inhibitors, macrosphelides H and L, from Periconia byssoides OUPS-N133
Takeshi Yamada, Masashi Iritani, Katsuhiko Minoura, Atsushi Numata, Yuichi Kobayashi, Yong-Gang Wang J Antibiot (Tokyo). 2002 Feb;55(2):147-54. doi: 10.7164/antibiotics.55.147.
Macrosphelide L has been isolated from a strain of Periconia byssoides originally separated from the sea hare Aplysia kurodai, and the absolute stereostructures of this material and macrosphelide H, previously undetermined, have been elucidated on the basis of spectroscopic analyses using 1D and 2D NMR techniques and some chemical transformation. (R)-Methyl 3-p-bromobenzoyloxy-5-oxohexanoate has been synthesized for configurational assignments of macrosphelide H. These macrosphelides inhibited the adhesion of human-leukemia HL-60 cells to HUVEC.
2. Rapid and transient intracellular oxidative stress due to novel macrosphelides trigger apoptosis via Fas/caspase-8-dependent pathway in human lymphoma U937 cells
Kanwal Ahmed, Qing-Li Zhao, Yuji Matsuya, Da-Yong Yu, Loreto B Feril Jr, Hideo Nemoto, Takashi Kondo Chem Biol Interact. 2007 Nov 20;170(2):86-99. doi: 10.1016/j.cbi.2007.07.007. Epub 2007 Jul 22.
The ability of the derivatives of macrosphelides (MS) core (simplified 16-membered core structure of natural MS) to induce apoptosis in human lymphoma U937 cells was investigated. Of the five compounds examined, MS core with ketones at 8 and 14 positions (MS5) showed the highest potency to induce apoptosis, while another, MS3 with one ketone, was minimal potent. MS5 was found to induce apoptosis in the U937 cells in a time- and dose-dependent fashion, as confirmed by DNA fragmentation analysis. MS5 treated cells showed increase in intracellular reactive oxygen species (ROS), glutathione depletion, Bid activation and lipid peroxidation. Pretreatment of cells with pancaspase inhibitor resulted in the complete inhibition of MS5-induced apoptosis. N-Acetyl-l-cysteine (NAC) pretreatment resulted in the increase in glutathione concentration, reduction of intracellular ROS, complete inhibition of DNA fragmentation, mitochondrial membrane potential (MMP) collapse, Fas externalization and caspase-8 activation. Furthermore, MS5-induced oxidative stress also triggered transient increase in intracellular calcium ion ([Ca2+]i) concentration which was completely inhibited by NAC. Pretreatment with an intracellular Ca2+ chelator, BAPTA-AM reduced MS5-induced DNA fragmentation and caspase-8 activation while it has marginal effects on MMP collapse. Taken together our present data showed that a rapid increase in intracellular ROS by MS5 triggers apoptosis via the Fas/caspase-8-mediated mitochondrial pathway suggesting that the presence of diketone makes the compound more potent to induce apoptosis. These characteristics of MS5 will make it useful for therapeutic applications of targeted apoptosis.
3. Mechanism of apoptosis induced by a newly synthesized derivative of macrosphelides with a thiazole side chain
Kanwal Ahmed, Yuji Matsuya, Hideo Nemoto, Syed Faisal Haider Zaidi, Toshiro Sugiyama, Yoko Yoshihisa, Tadamichi Shimizu, Takashi Kondo Chem Biol Interact. 2009 Feb 12;177(3):218-26. doi: 10.1016/j.cbi.2008.10.030. Epub 2008 Oct 30.
The apoptosis-inducing ability of hybrid compounds composed of macrosphelide and thiazole-containing side chain of epothilones was investigated. Among the tested series of hybrid compounds the one containing thiazole side chain at C15 (MSt-2) showed the maximum potency to induce apoptosis, while another containing thiazole side chain at C3 (MSt-6) was less potent. MSt-2 was found to induce apoptosis in human lymphoma (U937) cells in a dose- and time-dependent manner as confirmed by DNA fragmentation analysis. MSt-2 treated cells showed rapid reactive oxygen species (ROS) formation and c-Jun N-terminal kinase (JNK) activation. Furthermore, significant activation of extrinsic pathway as evident by Fas expression and caspase-8 activation was also observed. MSt-2-mediated decreased expression of Bid is an important event for cross talk between intrinsic and extrinsic signaling. N-acetyl-l-cysteine pre-treatment rescued cells from MSt-2-induced ROS formation, mitochondrial membrane potential (Delta psi(m)) loss, Fas expression, caspase-8 and -3 activation and DNA fragmentation. Moreover, antioxidant enzymes catalase and/or superoxide dismutase conjugated with polyethylene glycol also inhibit MSt-2-induced ROS formation, apoptosis and Delta psi(m) loss suggesting thereby pro-oxidant effects of MSt-2. Furthermore, JNK and pan-caspase inhibitors also protect cells from MSt-2-induced apoptosis. In addition to this, MSt-2 was found to be more potent in human colon carcinoma (HCT116) and human gastric cancer (AGS) cells while it has no effect on human normal dermal fibroblast. The important structure-activity relationship observed in the current study which makes MSt-2 more potent than MSt-6 is the position of thiazole side chain and stereochemistry of position 3 in chemical structure. In short the results of our study demonstrate that MSt-2-induced rapid ROS generation and mitochondrial dysfunction in cells trigger events responsible for mitochondria-dependent apoptosis pathway.
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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 ╳
