3895-92-9 Usage
Description
Chelerythrine Chloride, a naturally occurring alkaloid, is a potent and cell-permeable inhibitor of protein kinase C (PKC) with an IC50 value of 660 nM. It selectively targets the catalytic domain of PKC, regardless of the regulatory domain's attachment. As a competitive inhibitor concerning the phosphate acceptor and a non-competitive inhibitor concerning ATP, it is over ten times more potent than H-7, HCl. Chelerythrine Chloride also inhibits thromboxane formation and phosphoinositide metabolism in platelets. Additionally, it induces apoptotic DNA fragmentation and cell death in HL-60 human promyelocytic leukemia cells. It is a yellow to orange solid and has the ability to inhibit Bcl-xL function, displace Bax binding, and activate p38 MAP kinase and JUNK signaling pathways, leading to apoptosis in various cancer cell lines.
Uses
Used in Pharmaceutical Industry:
Chelerythrine Chloride is used as a research compound for its ability to inhibit protein kinase C, making it a valuable tool in studying the role of PKC in cellular processes and diseases. Its potent inhibition of PKC and induction of apoptosis in cancer cells also make it a potential candidate for the development of anticancer drugs.
Used in Cellular and Molecular Biology Research:
Chelerythrine Chloride is used as a specific inhibitor of protein kinase C in cellular and molecular biology research. It helps researchers understand the role of PKC in various cellular signaling pathways and its involvement in diseases such as cancer.
Used in Drug Discovery and Development:
Chelerythrine Chloride is used as a lead compound in drug discovery and development, particularly for the development of novel anticancer agents. Its ability to induce apoptosis in cancer cells and inhibit PKC makes it a promising starting point for the design of new therapeutics targeting cancer cell survival and proliferation.
Used in Platelet Research:
Chelerythrine Chloride is used as an inhibitor of thromboxane formation and phosphoinositide metabolism in platelets. This application aids in understanding the role of these processes in platelet function and their potential as therapeutic targets for conditions such as thrombosis and cardiovascular diseases.
Biochem/physiol Actions
Cell permeable: yes
references
1. j. m. herbert, j. m. augereau, j. gleye and j. p. maffrand, biochem biophys res commun 1990, 172, 993-999. 2. w. d. jarvis, a. j. turner, l. f. povirk, r. s. traylor and s. grant, cancer res 1994, 54, 1707-1714. 3. j. vrba, p. dolezel, j. vicar, m. modriansky and j. ulrichova, toxicol in vitro 2008, 22, 1008-1017. 4. m. vogler, k. weber, d. dinsdale, i. schmitz, k. schulze-osthoff, m. j. dyer and g. m. cohen, cell death differ 2009, 16, 1030-1039. 5. r. yu, s. mandlekar, t. h. tan and a. n. kong, j biol chem 2000, 275, 9612-9619. 6. s. yamamoto, k. seta, c. morisco, s. f. vatner and j. sadoshima, j mol cell cardiol 2001, 33, 1829-1848.
Check Digit Verification of cas no
The CAS Registry Mumber 3895-92-9 includes 7 digits separated into 3 groups by hyphens. The first part of the number,starting from the left, has 4 digits, 3,8,9 and 5 respectively; the second part has 2 digits, 9 and 2 respectively.
Calculate Digit Verification of CAS Registry Number 3895-92:
(6*3)+(5*8)+(4*9)+(3*5)+(2*9)+(1*2)=129
129 % 10 = 9
So 3895-92-9 is a valid CAS Registry Number.
InChI:InChI=1/C21H19NO4/c1-22-10-16-13(6-7-17(23-2)21(16)24-3)14-5-4-12-8-18-19(26-11-25-18)9-15(12)20(14)22/h4-10,12H,11H2,1-3H3
3895-92-9Relevant articles and documents
Structure and NMR properties of 6-substituted-5,6-dihydrobenzo[c] phenanthridine alkaloids
Kadam, Shivaji S.,Maier, Lukas,Solomek, Tomas,Necas, Marek,Smejkal, Karel,Dostal, Jiri,Sklenar, Vladimir,Marek, Radek
, p. 814 - 821 (2013)
We report a preparation of new 6-substituted-5,6-dihydrobenzo[c] phenanthridines by the reaction of azoles with quaternary benzo[c]phenanthridine alkaloids sanguinarine and chelerythrine. The prepared compounds have been characterized by NMR spectroscopy, mass spectrometry, and single-crystal X-ray diffraction. Conformational behaviors of carbazole derivatives in solution have been investigated by low-temperature NMR experiments. Barriers to rotation around newly formed C6-N bonds were determined to be 12-13 kcal/mol. Quantum chemical calculations have been used to reproduce the experimental observations. Large structural effects on several 1H NMR resonances were observed experimentally, analyzed by Density Functional Theory (DFT) calculations at B3LYP/6-311+G(d,p)/PCM level, and interpreted by ring-current effects of the benzo[c]phenanthridine and carbazole units. Copyright 2013 John Wiley & Sons, Ltd. Barrier to rotation around C-N bond was determined experimentally by low-temperature 1H NMR spectroscopy and calculated by using density functional theory (B3LYP/6-311+G(d,p)). Structural effects on selected 1H NMR resonances are rationalized by ring currents of benzo[c]phenanthridine and carbazole moieties. Copyright
Total synthesis of benzo[c]phenanthridine alkaloids based on a microwave-assisted electrocyclic reaction of the aza 6π-electron system and structural revision of broussonpapyrine
Ishihara, Yuhsuke,Azuma, Shuhei,Choshi, Tominari,Kohno, Kakujirou,Ono, Kanako,Tsutsumi, Hiroyuki,Ishizu, Takashi,Hibino, Satoshi
experimental part, p. 1320 - 1333 (2011/04/16)
Total syntheses of the des-N-methyl (nor) type of benzo[c]phenanthridine alkaloids 1a-f and 19 and benzo[c]phenanthridine alkaloids, chelerythrine (2d), and broussonpapyrine (2f) were achieved. The key step was the construction of tetracyclic 10,11-dihydrobenzo[c]phenanthridines using a microwave-assisted electrocyclic reaction of the 2-cycloalkenylbenzaldoxime methyl ether 4 as an aza 6π-electron system, which was derived in two steps from a Suzuki-Miyaura cross-coupling reaction of 2-bromobenzaldehyde 6 with 2-(3,4-dihydro-6,7- methylenedioxynaphthyl)boronic acid pinacol ester 7. In addition, the exact structure of broussonpapyrine (2f) (2,3,9,10-tetraoxygenated type) was determined to be chelerythrine (2d).
Total synthesis of chelerythrine, a benzo[c]phenanthridine alkaloid
Ishii,Ishikawa,Takeda,Suzuki,Harayaya
, p. 2002 - 2006 (2007/10/02)
By taking advantage of our novel synthetic methods involving CsF-mediated Claisen rearrangement of an aryl propargyl ether to a 2-methylbenzolfuran and oxidative cleavage of the furan ring to a salicylaldehyde, total synthesis of chelerythrine, a benzo[c]phenanthridine alkaloid, was accomplished via the common intermediate (5) prepared through the two routes shown in Chart 3.
